Advertisement

Case Studies

  • María Elena Álvarez-Buylla Roces
  • Juan Carlos Martínez-García
  • José Dávila-Velderrain
  • Elisa Domínguez-Hüttinger
  • Mariana Esther Martínez-Sánchez
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1069)

Abstract

The aim of this chapter is to illustrate the modeling procedures discussed in the previous chapter via three well-chosen examples.

References

  1. 1.
    Aberg, K. M., Man, M. Q., Gallo, R. L., Ganz, T., Crumrine, D., Brown, B. E., et al. (2008). Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers. Journal of Investigative Dermatology, 128(4), 917–925.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Abou-Jaoudé, W., Monteiro, P. T., Naldi, A., Grandclaudon, M., Soumelis, V., Chaouiya, C., et al. (2015). Model checking to assess T-helper cell plasticity. Frontiers in Bioengineering and Biotechnology, 2, 86.PubMedPubMedCentralGoogle Scholar
  3. 8.
    Albert, R., & Barabási, A. L. (2002). Statistical mechanics of complex networks. Reviews of Modern Physics, 74(1), 47.CrossRefGoogle Scholar
  4. 12.
    Aliahmadi, E., Gramlich, R., Grützkau, A., Hitzler, M., Krüger, M., Baumgrass, R., et al. (2009). TLR2-activated human Langerhans cells promote Th17 polarization via IL-1β, TGF-β and IL-23. European Journal of Immunology, 39(5), 1221–1230.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 15.
    Altrock, P. M., Liu, L. L., & Michor, F. (2015). The mathematics of cancer: Integrating quantitative models. Nature Reviews Cancer, 15(12), 730–745.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 16.
    Álvarez-Buylla, E. R., Azpeitia, E., Barrio, R., Benítez, M., & Padilla-Longoria, P. (2010). From ABC genes to regulatory networks, epigenetic landscapes and flower morphogenesis: Making biological sense of theoretical approaches. Seminars in Cell & Developmental Biology, 21(1), 108–117.CrossRefGoogle Scholar
  7. 17.
    Álvarez-Buylla, E. R., Benítez, M., Davila, E. B., Chaos, A., Espinosa-Soto, C., & Padilla-Longoria, P. (2007). Gene regulatory network models for plant development. Current Opinion in Plant Biology, 10(1), 83–91.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 18.
    Álvarez-Buylla, E. R., Chaos, Á., Aldana, M., Benítez, M., Cortes-Poza, Y., Espinosa-Soto, C., et al. (2008). Floral morphogenesis: Stochastic explorations of a gene network epigenetic landscape. PLoS One, 3(11), e3626.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 19.
    Álvarez-Buylla, E. R., Dávila-Velderrain, J., & Martínez-García, J. C. (2016). Systems biology approaches to development beyond bioinformatics: Nonlinear mechanistic models using plant systems. BioScience, 66(5), 371–383.CrossRefGoogle Scholar
  10. 20.
    Anand, P., Kunnumakara, A. B., Sundaram, C., Harikumar, K. B., Tharakan, S. T., Lai, O. S., et al. (2008). Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical Research, 25(9), 2097–2116.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 23.
    Antebi, Y. E., Nandagopal, N., & Elowitz, M. B. (2017). An operational view of intercellular signaling pathways. Current Opinion in Systems Biology, 1, 16–24.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 24.
    Ao, P., Galas, D., Hood, L., & Zhu, X. (2008). Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution. Medical Hypotheses, 70(3), 678–684.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 28.
    Azpeitia, E., Benítez, M., Padilla-Longoria, P., Espinosa-Soto, C., & Álvarez-Buylla, E. R. (2011). Dynamic network-based epistasis analysis: Boolean examples. Frontiers in Plant Science, 2, 92.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 29.
    Azpeitia, E., Benítez, M., Vega, I., Villarreal, C., & Álvarez-buylla, E. R. (2010). Single-cell and coupled GRN models of cell patterning in the Arabidopsis thaliana root stem cell niche. BMC Systems Biology, 4, 134.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 31.
    Azpeitia, E., Muñoz, S., González-Tokman, D., Martínez-Sánchez, M. E., Weinstein, N., Naldi, A., et al. (2017). The combination of the functionalities of feedback circuits is determinant for the attractors’ number and size in pathway-like Boolean networks. Scientific Reports, 7, 42023.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 33.
    Bäckman, A., Ny, A., Edlund, M., Ekholm, E., Hammarström, B. E., Törnell, J., et al. (2002). Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: A model for chronic itchy dermatitis. Journal of Investigative Dermatology, 118(3), 444–449.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 35.
    Baker, B. S. (2006). The role of microorganisms in atopic dermatitis. Clinical & Experimental Immunology, 144(1), 1–9.CrossRefGoogle Scholar
  18. 38.
    Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: Back to Virchow? The Lancet, 357(9255), 539–545.CrossRefGoogle Scholar
  19. 39.
    Balleza, E., Alvarez-Buylla, E. R., Chaos, A., Kauffman, S., Shmulevich, I., & Aldana, M. (2008). Critical dynamics in genetic regulatory networks: Examples from four kingdoms. PLoS One, 3(6), e2456.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 46.
    Battula, V. L., Evans, K. W., Hollier, B. G., Shi, Y., Marini, F. C., Ayyanan, A., et al. (2010). Epithelial-mesenchymal transition-derived cells exhibit multilineage differentiation potential similar to mesenchymal stem cells. Stem Cells, 28(8), 1435–1445.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 50.
    Benítez, M., Espinosa-Soto, C., Padilla-Longoria, P., Díaz, J., & Álvarez-Buylla, E. R. (2007). Equivalent genetic regulatory networks in different contexts recover contrasting spatial cell patterns that resemble those in Arabidopsis root and leaf epidermis: A dynamic model. The International Journal of Developmental Biology, 51, 139–155.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 51.
    Ben-Porath, I., Thomson, M. W., Carey, V. J., Ge, R., Bell, G. W., Regev, A., et al. (2008). An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nature Genetics, 40(5), 499–507.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 52.
    Bernard, F. X., Morel, F., Camus, M., Pedretti, N., Barrault, C., Garnier, J., et al. (2012). Keratinocytes under fire of proinflammatory cytokines: Bona fide innate immune cells involved in the physiopathology of chronic atopic dermatitis and psoriasis. Journal of Allergy, 2012, 10. Article ID 718725.Google Scholar
  24. 55.
    Bluestone, J. A., Mackay, C. R., O’shea, J. J., & Stockinger, B. (2009). The functional plasticity of T cell subsets. Nature Reviews Immunology, 9(11), 811–816.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 56.
    Bonelli, M., Shih, H. Y., Hirahara, K., Singelton, K., Laurence, A., Poholek, A., et al. (2014). Helper T cell plasticity: Impact of extrinsic and intrinsic signals on transcriptomes and epigenomes. In Transcriptional control of lineage differentiation in immune cells (pp. 279–326). Berlin: Springer International Publishing.Google Scholar
  26. 58.
    Boveri, T. (1914). The origin of malignant tumors (M. Boveri (1929) Baillière, Tindall & Cox, Trans.). Baltimore: The Williams and Wilkins Company.Google Scholar
  27. 60.
    Brattsand, M., Stefansson, K., Lundh, C., Haasum, Y., & Egelrud, T. (2005). A proteolytic cascade of kallikreins in the stratum corneum. Journal of Investigative Dermatology, 124(1), 198–203.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 62.
    Breitfeld, D., Ohl, L., Kremmer, E., Ellwart, J., Sallusto, F., Lipp, M., et al. (2000). Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. Journal of Experimental Medicine, 192(11), 1545–1552.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 65.
    Briot, A., Deraison, C., Lacroix, M., Bonnart, C., Robin, A., Besson, C., et al. (2009). Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. Journal of Experimental Medicine, 206(5), 1135–1147.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 66.
    Brown, S. J., Kroboth, K., Sandilands, A., Campbell, L. E., Pohler, E., Kezic, S., et al. (2012). Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose-dependent effect. Journal of Investigative Dermatology, 132(1), 98–104.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 68.
    Buddenkotte, J., Stroh, C., Engels, I. H., Moormann, C., Shpacovitch, V. M., Seeliger, S., et al. (2005). Agonists of proteinase-activated receptor-2 stimulate upregulation of intercellular cell adhesion molecule-1 in primary human keratinocytes via activation of NF-κB. Journal of Investigative Dermatology, 124(1), 38–45.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 73.
    Campisi, J., Andersen, J. K., Kapahi, P., & Melov, S. (2011). Cellular senescence: A link between cancer and age-related degenerative disease? Seminars in Cancer Biology, 21(6), 354–359.PubMedPubMedCentralGoogle Scholar
  33. 75.
    Cannons, J. L., Lu, K. T., & Schwartzberg, P. L. (2013). T follicular helper cell diversity and plasticity. Trends in Immunology, 34(5), 200–207.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 76.
    Caubet, C., Jonca, N., Brattsand, M., Guerrin, M., Bernard, D., Schmidt, R., et al. (2004). Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. Journal of Investigative Dermatology, 122(5), 1235–1244.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 83.
    Chen, C., & Wang, J. (2016). A physical mechanism of cancer heterogeneity. Scientific Reports, 6, 20679.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 87.
    Choi, M., Shi, J., Jung, S. H., Chen, X., & Cho, K. H. (2012). Attractor landscape analysis reveals feedback loops in the p53 network that control the cellular response to DNA damage. Science Signaling, 5(251), ra83.Google Scholar
  37. 88.
    Christodoulides, P., Hirata, Y., Domínguez-Hüttinger, E., Danby, S. G., Cork, M. J., Williams, H. C., et al. (2017). Computational design of treatment strategies for proactive therapy on atopic dermatitis using optimal control theory. Philosophical Transactions of the Royal Society A, 375(2096), 20160285.CrossRefGoogle Scholar
  38. 89.
    Ciofani, M., Madar, A., Galan, C., Sellars, M., Mace, K., Pauli, F., et al. (2012). A validated regulatory network for Th17 cell specification. Cell, 151(2), 289–303.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 90.
    Clark, W. H. (1995). The nature of cancer: Morphogenesis and progressive (self)-disorganization in neoplastic development and progression. Acta Oncologica, 34(1), 3–21.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 95.
    Cookson, W. (2004). The immunogenetics of asthma and eczema: A new focus on the epithelium. Nature Reviews Immunology, 4(12), 978–988.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 96.
    Coppé, J. P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., et al. (2008). Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biology, 6(12), e301.PubMedCentralCrossRefGoogle Scholar
  42. 98.
    Cork, M. J., Danby, S. G., Vasilopoulos, Y., Hadgraft, J., Lane, M. E., Moustafa, M., et al. (2009). Epidermal barrier dysfunction in atopic dermatitis. Journal of Investigative Dermatology, 129(8), 1892–1908.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 99.
    Cork, M. J., Robinson, D. A., Vasilopoulos, Y., Ferguson, A., Moustafa, M., MacGowan, A., et al. (2006). New perspectives on epidermal barrier dysfunction in atopic dermatitis: Gene–environment interactions. Journal of Allergy and Clinical Immunology, 118(1), 3–21.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 102.
    Creixell, P., Schoof, E. M., Erler, J. T., & Linding, R. (2012). Navigating cancer network attractors for tumor-specific therapy. Nature Biotechnology, 30(9), 842–848.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 103.
    Crotty, S. (2011). Follicular helper CD4 T cells (Tfh). Annual Review of Immunology, 29, 621–663.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 104.
    Cruickshanks, H. A., McBryan, T., Nelson, D. M., VanderKraats, N. D., Shah, P. P., Van Tuyn, J., et al. (2013). Senescent cells harbour features of the cancer epigenome. Nature Cell Biology, 15(12), 1495–1506.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 105.
    Csermely, P., & Korcsmáros, T. (2013). Cancer-related networks: A help to understand, predict and change malignant transformation. Seminars in Cancer Biology, 23(4), 209–212.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 106.
    Dai, L., Korolev, K. S., & Gore, J. (2013). Slower recovery in space before collapse of connected populations. Nature, 496(7445), 355–358.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 107.
    Danby, S. G., Chittock, J., Brown, K., Albenali, L. H., & Cork, M. J. (2014). The effect of tacrolimus compared with betamethasone valerate on the skin barrier in volunteers with quiescent atopic dermatitis. British Journal of Dermatology, 170(4), 914–921.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 108.
    Das, J., Chen, C. H., Yang, L., Cohn, L., Ray, P., & Ray, A. (2001). A critical role for NF-κB in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nature Immunology, 2(1), 45–50.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 109.
    Davila-Velderrain, J., & Álvarez-Buylla, E. R. (2014). Bridging genotype and phenotype. In Frontiers in ecology, evolution and complexity (pp. 144–154). Mexico: EditoraC3 CopIt-arXives, UNAM.Google Scholar
  52. 110.
    Davila-Velderrain, J., Juarez-Ramiro, L., Martinez-Garcia, J. C., Alvarez-Buylla, E. R. (2015). Methods for characterizing the epigenetic attractors landscape associated with Boolean gene regulatory networks. arXiv preprint. arXiv:1510.04230.Google Scholar
  53. 112.
    Davila-Velderrain, J., Villarreal, C., & Álvarez-Buylla, E. R. (2015). Reshaping the epigenetic landscape during early flower development: Induction of attractor transitions by relative differences in gene decay rates. BMC Systems Biology, 9(1), 20.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 113.
    De Benedetto, A., Kubo, A., & Beck, L. A. (2012). Skin barrier disruption: A requirement for allergen sensitization? Journal of Investigative Dermatology, 132(3), 949–963.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 114.
    De Craene, B., & Berx, G. (2013). Regulatory networks defining EMT during cancer initiation and progression. Nature Reviews Cancer, 13(2), 97–110.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 116.
    de Luis Balaguer, M. A., Fisher, A. P., Clark, N. M., Fernandez-Espinosa, M. G., Moller, B., Weijers, D., et al. (2017). An inference approach combines spatial and temporal gene expression data to predict gene regulatory networks in Arabidopsis stem cells. bioRxiv, 140269.Google Scholar
  57. 117.
    Demerjian, M., Hachem, J. P., Tschachler, E., Denecker, G., Declercq, W., Vandenabeele, P., et al. (2008). Acute modulations in permeability barrier function regulate epidermal cornification: Role of caspase-14 and the protease-activated receptor type 2. The American Journal of Pathology, 172(1), 86–97.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 118.
    Deraison, C., Bonnart, C., Lopez, F., Besson, C., Robinson, R., Jayakumar, A., et al. (2007). LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Molecular Biology of the Cell, 18(9), 3607–3619.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 120.
    Domínguez Hüttinger, E. (2014). Mathematical modelling of epithelium homeostasis (Doctoral dissertation, Imperial College London).Google Scholar
  60. 121.
    Dominguez-Hüttinger, E., Boon, N. J., Clarke, T. B., & Tanaka, R. J. (2017). Mathematical modelling of colonization, invasive infection and treatment of Streptococcus pneumoniae. Frontiers in Physiology, 8, 115.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 122.
    Domínguez-Hüttinger, E., Christodoulides, P., Miyauchi, K., Irvine, A. D., Okada-Hatakeyama, M., Kubo, M., et al. (2017). Mathematical modeling of atopic dermatitis reveals “double-switch” mechanisms underlying 4 common disease phenotypes. Journal of Allergy and Clinical Immunology, 139(6), 1861–1872.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 123.
    Domínguez-Hüttinger, E., Ono, M., Barahona, M., & Tanaka, R. J. (2013). Risk factor-dependent dynamics of atopic dermatitis: Modelling multi-scale regulation of epithelium homeostasis. Interface Focus, 3(2), 20120090.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 124.
    Dommisch, H., Chung, W. O., Rohani, M. G., Williams, D., Rangarajan, M., Curtis, M. A., et al. (2007). Protease-activated receptor 2 mediates human beta-defensin 2 and CC chemokine ligand 20 mRNA expression in response to proteases secreted by Porphyromonas gingivalis. Infection and Immunity, 75(9), 4326–4333.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 126.
    Duhen, T., Duhen, R., Lanzavecchia, A., Sallusto, F., & Campbell, D. J. (2012). Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells. Blood, 119(19), 4430–4440.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 127.
    DuPage, M., & Bluestone, J. A. (2016). Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease. Nature Reviews Immunology, 16(3), 149–163.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 128.
    Ehlken, B., Mḧrenschlager, M., Kugland, B., Berger, K., Quednau, K., & Ring, J. (2005). Cost-of-illness study in patients suffering from atopic eczema in Germany. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete, 56(12), 1144–1151.Google Scholar
  67. 130.
    Elias, P. M., Ahn, S. K., Denda, M., Brown, B. E., Crumrine, D., Kimutai, L. K., et al. (2002). Modulations in epidermal calcium regulate the expression of differentiation-specific markers. Journal of Investigative Dermatology, 119(5), 1128–1136.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 131.
    Elias, P. M., Brown, B. E., Crumrine, D., Feingold, K. R., & Ahn, S. K. (2002). Origin of the epidermal calcium gradient: Regulation by barrier status and role of active vs passive mechanisms. Journal of Investigative Dermatology, 119(6), 1269–1274.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 133.
    Elias, P. M., & Schmuth, M. (2009). Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Current Allergy and Asthma Reports, 9(4), 265–272.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 134.
    Elias, P. M., & Wakefield, J. S. (2011). Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis. Clinical Reviews in Allergy & Immunology, 41(3), 282–295.CrossRefGoogle Scholar
  71. 136.
    Ellis, C. N., Drake, L. A., Prendergast, M. M., Abramovits, W., Boguniewicz, M., Daniel, C. R., et al. (2002). Cost of atopic dermatitis and eczema in the United States. Journal of the American Academy of Dermatology, 46(3), 361–370.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 137.
    Ellmeier, W., & Taniuchi, I. (Eds.). (2014). Transcriptional control of lineage differentiation in immune cells (Vol. 381). Berlin: Springer.Google Scholar
  73. 140.
    Enciso, J., Álvarez-Buylla, E., & Pelayo, R. (2017). A multi-modular Boolean network for the study of acute lymphoblastic leukemia. Experimental Hematology, 53, S109.CrossRefGoogle Scholar
  74. 141.
    Espinosa-Soto, C., Padilla-Longoria, P., & Álvarez-Buylla, E. R. (2004). A gene regulatory network model for cell–fate determination during Arabidopsis thaliana flower development that is robust and recovers experimental gene expression profiles. Plant Cell, 16, 2923–2939.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 142.
    Ewald, J. A., Desotelle, J. A., Wilding, G., & Jarrard, D. F. (2010). Therapy-induced senescence in cancer. Journal of the National Cancer Institute, 102(20), 1536–1546.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 143.
    Fallon, P. G., Sasaki, T., Sandilands, A., Campbell, L. E., Saunders, S. P., Mangan, N. E., et al. (2009). A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nature Genetics, 41(5), 602–608.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 145.
    Feinberg, A. P., Koldobskiy, M. A., & Göndör, A. (2016). Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nature Reviews Genetics, 17(5), 284–299.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 151.
    Foo, J., Leder, K., & Michor, F. (2011). Stochastic dynamics of cancer initiation. Physical Biology, 8(1), 015002.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 152.
    Fortugno, P., Furio, L., Teson, M., Berretti, M., El Hachem, M., Zambruno, G., et al. (2012). The 420K LEKTI variant alters LEKTI proteolytic activation and results in protease deregulation: Implications for atopic dermatitis. Human Molecular Genetics, 21(19), 4187–4200.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 155.
    Friend, S. H., Dryja, T. P., & Weinberg, R. A. (1988). Oncogenes and tumor-suppressing genes. New England Journal of Medicine, 318(10), 618–622.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 156.
    Fry, L. (2003). An atlas of atopic eczema. Boca Raton: Parthenon.CrossRefGoogle Scholar
  82. 158.
    Galic, S., Sachithanandan, N., Kay, T. W., & Steinberg, G. R. (2014). Suppressor of cytokine signalling (SOCS) proteins as guardians of inflammatory responses critical for regulating insulin sensitivity. Biochemical Journal, 461(2), 177–188.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 160.
    Galli, S. J., Tsai, M., & Piliponsky, A. M. (2008). The development of allergic inflammation. Nature, 454(7203), 445–454.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 162.
    Garbe, J. C., Vrba, L., Sputova, K., Fuchs, L., Novak, P., Brothman, A. R., et al. (2014). Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations. Cell Cycle, 13(21), 3423–3435.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 164.
    Garraway, L. A., & Lander, E. S. (2013). Lessons from the cancer genome. Cell, 153(1), 17–37.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 165.
    Geginat, J., Paroni, M., Facciotti, F., Gruarin, P., Kastirr, I., Caprioli, F., et al. (2013). The CD4-centered universe of human T cell subsets. Seminars in Immunology, 25(4), 252–262. New York: Academic.Google Scholar
  87. 166.
    Gene Ontology Consortium. (2004). The Gene Ontology (GO) database and informatics resource. Nucleic Acids Research, 32(Suppl. 1), D258–D261.CrossRefGoogle Scholar
  88. 168.
    Gittler, J. K., Shemer, A., Suárez-Fariñas, M., Fuentes-Duculan, J., Gulewicz, K. J., Wang, C. Q., et al. (2012). Progressive activation of T H 2/T H 22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. Journal of Allergy and Clinical Immunology, 130(6), 1344–1354.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 175.
    Goswami, R., & Kaplan, M. H. (2011). A brief history of IL-9. The Journal of Immunology, 186(6), 3283–3288.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 176.
    Gould, H. J., & Sutton, B. J. (2008). IgE in allergy and asthma today. Nature Reviews Immunology, 8(3), 205–217.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 179.
    Grazia Roncarolo, M., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K., & Levings, M. K. (2006). Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunological Reviews, 212(1), 28–50.CrossRefGoogle Scholar
  92. 182.
    Grosso, G., Bella, F., Godos, J., Sciacca, S., Del Rio, D., Ray, S., et al. (2017). Possible role of diet in cancer: Systematic review and multiple meta-analyses of dietary patterns, lifestyle factors, and cancer risk. Nutrition Reviews, 75(6), 405–419.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 184.
    Hachem, J. P., Crumrine, D., Fluhr, J., Brown, B. E., Feingold, K. R., & Elias, P. M. (2003). pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. Journal of Investigative Dermatology, 121(2), 345–353.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 185.
    Hachem, J. P., Houben, E., Crumrine, D., Man, M. Q., Schurer, N., Roelandt, T., et al. (2006). Serine protease signaling of epidermal permeability barrier homeostasis. Journal of Investigative Dermatology, 126(9), 2074–2086.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 186.
    Hahn, W. C., & Weinberg, R. A. (2002). Rules for making human tumor cells. New England Journal of Medicine, 347(20), 1593–1603.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 188.
    Ham, H. J., Andeweg, A. C., & Boer, R. J. (2013). Induction of appropriate Th-cell phenotypes: Cellular decision-making in heterogeneous environments. Parasite Immunology, 35(11), 318–330.PubMedPubMedCentralGoogle Scholar
  97. 190.
    Hammad, H., & Lambrecht, B. N. (2008). Dendritic cells and epithelial cells: Linking innate and adaptive immunity in asthma. Nature Reviews Immunology, 8(3), 193–204.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 191.
    Han, J. M., Patterson, S. J., Speck, M., Ehses, J. A., & Levings, M. K. (2014). Insulin inhibits IL-10-mediated regulatory T cell function: Implications for obesity. The Journal of Immunology, 192(2), 623–629.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 192.
    Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674.CrossRefGoogle Scholar
  100. 193.
    Hansemann, D. (1890). Ueber asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung. Virchows Archiv, 119(2), 299–326.CrossRefGoogle Scholar
  101. 198.
    Hirata, Y., Bruchovsky, N., & Aihara, K. (2010). Development of a mathematical model that predicts the outcome of hormone therapy for prostate cancer. Journal of Theoretical Biology, 264(2), 517–527.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 200.
    Hirata, Y., Morino, K., Akakura, K., Higano, C. S., Bruchovsky, N., Gambol, T., et al. (2015). Intermittent androgen suppression: Estimating parameters for individual patients based on initial PSA data in response to androgen deprivation therapy. PloS One, 10(6), e0130372.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 201.
    Höfer, T., Nathansen, H., Löhning, M., Radbruch, A., & Heinrich, R. (2002). GATA-3 transcriptional imprinting in Th2 lymphocytes: A mathematical model. Proceedings of the National Academy of Sciences, 99(14), 9364–9368.CrossRefGoogle Scholar
  104. 202.
    Hoffman, D. R., Kroll, L. M., Basehoar, A., Reece, B., Cunningham, C. T., & Koenig, D. W. (2014). Immediate and extended effects of sodium lauryl sulphate exposure on stratum corneum natural moisturizing factor. International Journal of Cosmetic Science, 36(1), 93–101.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 203.
    Hoffman, D. R., Kroll, L. M., Basehoar, A., Reece, B., Cunningham, C. T., & Koenig, D. W. (2015). Immediate and extended effects of abrasion on stratum corneum natural moisturizing factor. Skin Research and Technology, 21(3), 366–372.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 204.
    Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991). p53 mutations in human cancers. Science, 253(5015), 49–53.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 206.
    Horimukai, K., Morita, K., Narita, M., Kondo, M., Kitazawa, H., Nozaki, M., et al. (2014). Application of moisturizer to neonates prevents development of atopic dermatitis. Journal of Allergy and Clinical Immunology, 134(4), 824–830.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 207.
    Horn, H., Lawrence, M. S., Chouinard, C. R., Shrestha, Y., Hu, J. X., Worstell, E., et al. (2017). Expanding discovery from cancer genomes by integrating protein network analyses with in vivo tumorigenesis assays. bioRxiv, 151977.Google Scholar
  109. 208.
    Hovnanian, A. (2013). Netherton syndrome: Skin inflammation and allergy by loss of protease inhibition. Cell and Tissue Research, 351(2), 289–300.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 209.
    Howell, M. D., Kim, B. E., Gao, P., Grant, A. V., Boguniewicz, M., DeBenedetto, A., et al. (2007). Cytokine modulation of atopic dermatitis filaggrin skin expression. Journal of Allergy and Clinical Immunology, 120(1), 150–155.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 210.
    Howes, A., Stimpson, P., Redford, P., Gabrysova, L., & O’Garra, A. (2014). Interleukin-10: Cytokines in anti-inflammation and tolerance. In Cytokine frontiers (pp. 327–352). Tokyo: Springer.CrossRefGoogle Scholar
  112. 211.
    Huang, S. (2011). Systems biology of stem cells: Three useful perspectives to help overcome the paradigm of linear pathways. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 366(1575), 2247–2259.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 212.
    Huang, S. (2011). On the intrinsic inevitability of cancer: From foetal to fatal attraction. Seminars in Cancer Biology, 21(3), 183–199.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 213.
    Huang, S. (2013). Genetic and non-genetic instability in tumor progression: Link between the fitness landscape and the epigenetic landscape of cancer cells. Cancer and Metastasis Reviews, 32(3–4), 423–448.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 214.
    Huang, S., Eichler, G., Bar-Yam, Y., & Ingber, D. E. (2005). Cell fates as high-dimensional attractor states of a complex gene regulatory network. Physical Review Letters, 94(12), 128701.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 216.
    Huang, S., & Ingber, D. E. (2007). A non-genetic basis for cancer progression and metastasis: Self-organizing attractors in cell regulatory networks. Breast Disease, 26(1), 27–54.CrossRefGoogle Scholar
  117. 217.
    Huang, S., & Kauffman, S. A. (2009). Complex GRN regulatory networks: From structure to biological observables: Cell fate determination. In Encyclopedia of complexity and systems science (pp. 1180–1213). New York: Springer.CrossRefGoogle Scholar
  118. 219.
    Hudson, T. J., Anderson, W., Aretz, A., Barker, A. D., Bell, C., Bernabé, R. R., et al. (2010). International network of cancer genome projects. Nature, 464(7291), 993–998.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 222.
    Irvine, A. D., McLean, W. I., & Leung, D. Y. (2011). Filaggrin mutations associated with skin and allergic diseases. New England Journal of Medicine, 365(14), 1315–1327.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 223.
    Ivanova, E. A., & Orekhov, A. N. (2015). T helper lymphocyte subsets and plasticity in autoimmunity and cancer: An overview. BioMed Research International, 2015, 9. Article ID 327470.Google Scholar
  121. 231.
    Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y., & Morishima, K. (2017). KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Research, 45(D1), D353–D361.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 233.
    Kaneko, K. (2011). Characterization of stem cells and cancer cells on the basis of gene expression profile stability, plasticity, and robustness. Bioessays, 33(6), 403–413.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 234.
    Kanno, Y., Vahedi, G., Hirahara, K., Singleton, K., & O’Shea, J. J. (2012). Transcriptional and epigenetic control of T helper cell specification: Molecular mechanisms underlying commitment and plasticity. Annual Review of Immunology, 30, 707–731.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 236.
    Kaplan, D. H., Igyártó, B. Z., & Gaspari, A. A. (2012). Early immune events in the induction of allergic contact dermatitis. Nature Reviews Immunology, 12(2), 114–124.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 237.
    Kaplan, M. H. (2013). Th9 cells: Differentiation and disease. Immunological Reviews, 252(1), 104–115.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 238.
    Kauffman, S. (1971). Gene regulation networks: A theory for their global structure and behaviors. Current Topics in Developmental Biology, 6, 145–182.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 240.
    Kauffman, S. A. (1969). Metabolic stability and epigenesis in randomly constructed genetic nets. Journal of Theoretical Biology, 22(3), 437–467.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 242.
    Kawasaki, H., Nagao, K., Kubo, A., Hata, T., Shimizu, A., Mizuno, H., et al. (2012). Altered stratum corneum barrier and enhanced percutaneous immune responses in filaggrin-null mice. Journal of Allergy and Clinical Immunology, 129(6), 1538–1546.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 245.
    Kezic, S., O’regan, G. M., Yau, N., Sandilands, A., Chen, H., Campbell, L. E., et al. (2011). Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy, 66(7), 934–940.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 248.
    Kleinewietfeld, M., & Hafler, D. A. (2013). The plasticity of human Treg and Th17 cells and its role in autoimmunity. Seminars in Immunology, 25(4), 305–312.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 249.
    Knosp, C. A., & Johnston, J. A. (2012). Regulation of CD4+ T-cell polarization by suppressor of cytokine signalling proteins. Immunology, 135(2), 101–111.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 250.
    Komatsu, N., Saijoh, K., Kuk, C., Liu, A. C., Khan, S., Shirasaki, F., et al. (2007). Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients. Experimental Dermatology, 16(6), 513–519.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 251.
    Kong, H. H., Oh, J., Deming, C., Conlan, S., Grice, E. A., Beatson, M. A., et al. (2012). Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Research, 22(5), 850–859.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 252.
    Krogan, N. J., Lippman, S., Agard, D. A., Ashworth, A., & Ideker, T. (2015). The cancer cell map initiative: Defining the hallmark networks of cancer. Molecular Cell, 58(4), 690–698.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 253.
    Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., et al. (2015). Integrative analysis of 111 reference human epigenomes. Nature, 518(7539), 317–330.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 254.
    Kundu, J. K., & Surh, Y. J. (2008). Inflammation: Gearing the journey to cancer. Mutation Research/Reviews in Mutation Research, 659(1), 15–30.CrossRefGoogle Scholar
  137. 255.
    Kuo, I. H., Yoshida, T., De Benedetto, A., & Beck, L. A. (2013). The cutaneous innate immune response in patients with atopic dermatitis. Journal of Allergy and Clinical Immunology, 131(2), 266–278.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 257.
    Lambrecht, B. N., & Hammad, H. (2010). The role of dendritic and epithelial cells as master regulators of allergic airway inflammation. The Lancet, 376(9743), 835–843.CrossRefGoogle Scholar
  139. 259.
    Land, H., Parada, L. F., & Weinberg, R. A. (1983). Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature, 304(5927), 596–602.PubMedCrossRefGoogle Scholar
  140. 260.
    Lasry, A., & Ben-Neriah, Y. (2015). Senescence-associated inflammatory responses: Aging and cancer perspectives. Trends in Immunology, 36(4), 217–228.PubMedCrossRefPubMedCentralGoogle Scholar
  141. 262.
    Lathia, J. D., Mack, S. C., Mulkearns-Hubert, E. E., Valentim, C. L., & Rich, J. N. (2015). Cancer stem cells in glioblastoma. Genes & Development, 29(12), 1203–1217.CrossRefGoogle Scholar
  142. 266.
    Lee, S. E., Kim, J. M., Jeong, S. K., Jeon, J. E., Yoon, H. J., Jeong, M. K., et al. (2010). Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes. Archives of Dermatological Research, 302(10), 745–756.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 268.
    Lee, Y. K., Mukasa, R., Hatton, R. D., & Weaver, C. T. (2009). Developmental plasticity of Th17 and Treg cells. Current Opinion in Immunology, 21(3), 274–280.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 269.
    Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1998). Genetic instabilities in human cancers. Nature, 396(6712), 643–649.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 270.
    Leung, D. Y. (2000). Atopic dermatitis: New insights and opportunities for therapeutic intervention. Journal of Allergy and Clinical Immunology, 105(5), 860–876.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 272.
    Li, C., & Wang, J. (2013). Quantifying cell fate decisions for differentiation and reprogramming of a human stem cell network: Landscape and biological paths. PLoS Computational Biology, 9(8), e1003165.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 273.
    Li, C., & Wang, J. (2014). Quantifying the underlying landscape and paths of cancer. Journal of the Royal Society Interface, 11(100), 20140774.PubMedCentralCrossRefGoogle Scholar
  148. 274.
    Li, C. W., Xia, W., Huo, L., Lim, S. O., Wu, Y., Hsu, J. L., et al. (2012). Epithelial–mesenchymal transition induced by TNF-α requires NF-κB-mediated transcriptional upregulation of Twist1. Cancer Research, 72(5), 1290–1300.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 280.
    Liston, A., & Gray, D. H. (2014). Homeostatic control of regulatory T cell diversity. Nature Reviews Immunology, 14(3), 154–165.PubMedCrossRefGoogle Scholar
  150. 283.
    Liu, Z., Li, Z., Mao, K., Zou, J., Wang, Y., Tao, Z., et al. (2009). Dec2 promotes Th2 cell differentiation by enhancing IL-2R signaling. The Journal of Immunology, 183(10), 6320–6329.PubMedCrossRefGoogle Scholar
  151. 285.
    Loeb, L. A., & Harris, C. C. (2008). Advances in chemical carcinogenesis: A historical review and prospective. Cancer Research, 68(17), 6863–6872.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 287.
    Longo, V. D., & Fontana, L. (2010). Calorie restriction and cancer prevention: Metabolic and molecular mechanisms. Trends in Pharmacological Sciences, 31(2), 89–98.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 288.
    Longo, V. D., & Mattson, M. P. (2014). Fasting: Molecular mechanisms and clinical applications. Cell Metabolism, 19(2), 181–192.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 290.
    Lu, Y., Hong, S., Li, H., Park, J., Hong, B., Wang, L., et al. (2012). Th9 cells promote antitumor immune responses in vivo. The Journal of Clinical Investigation, 122(11), 4160.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 292.
    MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013). Metabolic regulation of T lymphocytes. Annual Review of Immunology, 31, 259–283.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 293.
    Magi, S., Iwamoto, K., & Okada-Hatakeyama, M. (2017). Current status of mathematical modeling of cancer – From the viewpoint of cancer hallmarks. Current Opinion in Systems Biology, 2, 39–48.CrossRefGoogle Scholar
  157. 294.
    Mahalingam, D., Kong, C. M., Lai, J., Tay, L. L., Yang, H., & Wang, X. (2012). Reversal of aberrant cancer methylome and transcriptome upon direct reprogramming of lung cancer cells. Scientific Reports, 2, 592.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 296.
    Man, M. Q., Hatano, Y., Lee, S. H., Man, M., Chang, S., Feingold, K. R., et al. (2008). Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: Structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. Journal of Investigative Dermatology, 128(1), 79–86.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 297.
    Mancini, A. J., Kaulback, K., & Chamlin, S. L. (2008). The socioeconomic impact of atopic dermatitis in the United States: A systematic review. Pediatric Dermatology, 25(1), 1–6.PubMedCrossRefPubMedCentralGoogle Scholar
  160. 298.
    Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., et al. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704–715.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 303.
    Martinez-Sanchez, M. E., Mendoza, L., Villarreal, C., & Álvarez-Buylla, E. R. (2015). A minimal regulatory network of extrinsic and intrinsic factors recovers observed patterns of CD4+ T cell differentiation and plasticity. PLoS Computational Biology, 11(6), e1004324.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 306.
    McAleer, M. A., & Irvine, A. D. (2013). The multifunctional role of filaggrin in allergic skin disease. Journal of Allergy and Clinical Immunology, 131(2), 280–291.PubMedCrossRefPubMedCentralGoogle Scholar
  163. 309.
    McGirt, L. Y., & Beck, L. A. (2006). Innate immune defects in atopic dermatitis. Journal of Allergy and Clinical Immunology, 118(1), 202–208.PubMedCrossRefPubMedCentralGoogle Scholar
  164. 310.
    McLaughlin, T., Liu, L. F., Lamendola, C., Shen, L., Morton, J., Rivas, H., et al. (2014). T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(12), 2637–2643.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 316.
    Méndez-López, L. F., Davila-Velderrain, J., Domínguez-Hüttinger, E., Enríquez-Olguín, C., Martínez-García, J. C., & Álvarez-Buylla, E. R. (2017). Gene regulatory network underlying the immortalization of epithelial cells. BMC Systems Biology, 11(1), 24.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 317.
    Mendoza, L. (2006). A network model for the control of the differentiation process in Th cells. Biosystems, 84(2), 101–114.PubMedCrossRefPubMedCentralGoogle Scholar
  167. 318.
    Mendoza, L., & Álvarez-Buylla, E. R. (1998). Dynamics of the genetic regulatory network for arabidopsis thaliana flower morphogenesis. Journal of Theoretical Biology, 193(2), 307–319.PubMedCrossRefPubMedCentralGoogle Scholar
  168. 320.
    Mendoza, L., Thieffry, D., & Álvarez-Buylla, E. R. (1999). Genetic control of flower morphogenesis in Arabidopsis thaliana: A logical analysis. Bioinformatics, 15, 593–606.PubMedCrossRefPubMedCentralGoogle Scholar
  169. 322.
    Micalizzi, D. S., Farabaugh, S. M., & Ford, H. L. (2010). Epithelial-mesenchymal transition in cancer: Parallels between normal development and tumor progression. Journal of Mammary Gland Biology and Neoplasia, 15(2), 117–134.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 323.
    Milanovic, M., Fan, D. N., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., et al. (2018). Senescence-associated reprogramming promotes cancer stemness. Nature, 553, 96–100.PubMedCrossRefPubMedCentralGoogle Scholar
  171. 325.
    Milo, R., Shen-Orr, S., Itzkovitz, S., Kashtan, N., Chklovskii, D., & Alon, U. (2002). Network motifs: Simple building blocks of complex networks. Science, 298(5594), 824–827.PubMedCrossRefPubMedCentralGoogle Scholar
  172. 329.
    Morel, A. P., Lièvre, M., Thomas, C., Hinkal, G., Ansieau, S., & Puisieux, A. (2008). Generation of breast cancer stem cells through epithelial-mesenchymal transition. PloS One, 3(8), e2888.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 331.
    Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A., & Coffman, R. L. (1986). Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. The Journal of Immunology, 136(7), 2348–2357.PubMedPubMedCentralGoogle Scholar
  174. 333.
    Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., et al. (2013). Programmed cell senescence during mammalian embryonic development. Cell, 155(5), 1104–1118.PubMedCrossRefPubMedCentralGoogle Scholar
  175. 334.
    Murphy, K. M., & Stockinger, B. (2010). Effector T cell plasticity: Flexibility in the face of changing circumstances. Nature Immunology, 11(8), 674–680.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 337.
    Myers, J. M. B., Martin, L. J., Kovacic, M. B., Mersha, T. B., He, H., Pilipenko, V., et al. (2014). Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma. Journal of Allergy and Clinical Immunology, 134(4), 891–899.CrossRefGoogle Scholar
  177. 338.
    Nakamura, Y., Oscherwitz, J., Cease, K. B., Chan, S. M., Muñoz-Planillo, R., Hasegawa, M., et al. (2013). Staphylococcus δ-toxin induces allergic skin disease by activating mast cells. Nature, 503(7476), 397–401.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 339.
    Nakayamada, S., Takahashi, H., Kanno, Y., & O’Shea, J. J. (2012). Helper T cell diversity and plasticity. Current Opinion in Immunology, 24(3), 297–302.PubMedPubMedCentralCrossRefGoogle Scholar
  179. 340.
    Naldi, A., Berenguier, D., Fauré, A., Lopez, F., Thieffry, D., & Chaouiya, C. (2009). Logical modelling of regulatory networks with GINsim 2.3. Biosystems, 97(2), 134–139.PubMedCrossRefPubMedCentralGoogle Scholar
  180. 341.
    Naldi, A., Carneiro, J., Chaouiya, C., & Thieffry, D. (2010). Diversity and plasticity of Th cell types predicted from regulatory network modelling. PLoS Computational Biology, 6(9), e1000912.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 342.
    Naldi, A., Monteiro, P. T., Müssel, C., Consortium for Logical Models and Tools, Kestler, H. A., Thieffry, D., et al. (2015). Cooperative development of logical modelling standards and tools with CoLoMoTo. Bioinformatics, 31(7), 1154–1159.CrossRefGoogle Scholar
  182. 345.
    Nestle, F. O., Di Meglio, P., Qin, J. Z., & Nickoloff, B. J. (2009). Skin immune sentinels in health and disease. Nature Reviews Immunology, 9(10), 679–691.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 347.
    Newell, L., Polak, M. E., Perera, J., Owen, C., Boyd, P., Pickard, C., et al. (2013). Sensitization via healthy skin programs Th2 responses in individuals with atopic dermatitis. Journal of Investigative Dermatology, 133(10), 2372–2380.PubMedCrossRefPubMedCentralGoogle Scholar
  184. 349.
    Nnoruka, E. N., & Dermatology London Clinic. (2004). Tropical medicine rounds current epidemiology of atopic dermatitis in south-eastern Nigeria International Journal of Dermatology, 43(10), 739–744. Wiley online library, ISSN:1365-4632.Google Scholar
  185. 350.
    Nograles, K. E., Zaba, L. C., Guttman-Yassky, E., Fuentes-Duculan, J., Suárez-Fariñas, M., Cardinale, I., et al. (2008). Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. British Journal of Dermatology, 159(5), 1092–1102.PubMedPubMedCentralGoogle Scholar
  186. 351.
    Norris, D. A. (2005). Mechanisms of action of topical therapies and the rationale for combination therapy. Journal of the American Academy of Dermatology, 53(1), S17–S25.PubMedCrossRefPubMedCentralGoogle Scholar
  187. 352.
    Nuorti, J. P., Butler, J. C., Crutcher, J. M., Guevara, R., Welch, D., Holder, P., et al. (1998). An outbreak of multidrug-resistant pneumococcal pneumonia and bacteremia among unvaccinated nursing home residents. New England Journal of Medicine, 338(26), 1861–1868.PubMedCrossRefPubMedCentralGoogle Scholar
  188. 354.
    Olefsky, J. M., & Glass, C. K. (2010). Macrophages, inflammation, and insulin resistance. Annual Review of Physiology, 72, 219–246.PubMedCrossRefPubMedCentralGoogle Scholar
  189. 356.
    O’regan, G. M., Sandilands, A., McLean, W. I., & Irvine, A. D. (2009). Filaggrin in atopic dermatitis. Journal of Allergy and Clinical Immunology, 124(3), R2–R6.PubMedCrossRefPubMedCentralGoogle Scholar
  190. 357.
    O’Shea, J. J., Gadina, M., & Kanno, Y. (2011). Cytokine signaling: Birth of a pathway. The Journal of Immunology, 187(11), 5475–5478.PubMedCrossRefPubMedCentralGoogle Scholar
  191. 358.
    O’Shea, J. J., & Paul, W. E. (2010). Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science, 327(5969), 1098–1102.PubMedPubMedCentralCrossRefGoogle Scholar
  192. 361.
    Palmer, C. N., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., et al. (2006). Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics, 38(4), 441–446.PubMedCrossRefPubMedCentralGoogle Scholar
  193. 364.
    Paternoster, L., Standl, M., Waage, J., Baurecht, H., Hotze, M., Strachan, D. P., et al. (2015). Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nature Genetics, 47(12), 1449–1456.PubMedPubMedCentralCrossRefGoogle Scholar
  194. 367.
    Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., et al. (2008). Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metabolism, 8(2), 157–168.PubMedPubMedCentralCrossRefGoogle Scholar
  195. 369.
    Pérez-Ruiz, R. V., García-Ponce, B., Marsch-Martínez, N., Ugartechea-Chirino, Y., Villajuana-Bonequi, M., de Folter, S., et al. (2015). XAANTAL2 (AGL14) is an important component of the complex gene regulatory network that underlies Arabidopsis shoot apical meristem transitions. Molecular Plant, 8(5), 796–813.PubMedCrossRefPubMedCentralGoogle Scholar
  196. 375.
    Polak, P., Karlić, R., Koren, A., Thurman, R., Sandstrom, R., Lawrence, M. S., et al. (2015). Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature, 518(7539), 360–364.PubMedPubMedCentralCrossRefGoogle Scholar
  197. 377.
    Prina, E., Ranzani, O. T., & Torres, A. (2015). Community-acquired pneumonia. The Lancet, 386(9998), 1097–1108.CrossRefGoogle Scholar
  198. 382.
    Quail, D. F., Olson, O. C., Bhardwaj, P., Walsh, L. A., Akkari, L., Quick, M. L., et al. (2017). Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nature Cell Biology, 19(8), ncb3578.Google Scholar
  199. 383.
    Radisky, D. C., & LaBarge, M. A. (2008). Epithelial-mesenchymal transition and the stem cell phenotype. Cell Stem Cell, 2(6), 511–512.PubMedCrossRefPubMedCentralGoogle Scholar
  200. 387.
    Ring, J., Alomar, A., Bieber, T., Deleuran, M., Fink-Wagner, A., Gelmetti, C., et al. (2012). Guidelines for treatment of atopic eczema (atopic dermatitis) Part I. Journal of the European Academy of Dermatology and Venereology, 26(8), 1045–1060.PubMedCrossRefPubMedCentralGoogle Scholar
  201. 388.
    Rivera, C. M., & Ren, B. (2013). Mapping human epigenomes. Cell, 155(1), 39–55.PubMedCrossRefPubMedCentralGoogle Scholar
  202. 389.
    Roedl, D., Traidl-Hoffmann, C., Ring, J., Behrendt, H., & Braun-Falco, M. (2009). Serine protease inhibitor lymphoepithelial Kazal type-related inhibitor tends to be decreased in atopic dermatitis. Journal of the European Academy of Dermatology and Venereology, 23(11), 1263.PubMedCrossRefPubMedCentralGoogle Scholar
  203. 390.
    Roekevisch, E., Spuls, P. I., Kuester, D., Limpens, J., & Schmitt, J. (2014). Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: A systematic review. Journal of Allergy and Clinical Immunology, 133(2), 429–438.PubMedCrossRefPubMedCentralGoogle Scholar
  204. 393.
    Rubin, H. (1985). Cancer as a dynamic developmental disorder. Cancer Research, 45(7), 2935–2942.PubMedPubMedCentralGoogle Scholar
  205. 396.
    Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., & Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. The Journal of Immunology, 155(3), 1151–1164.PubMedPubMedCentralGoogle Scholar
  206. 397.
    Sandilands, A., Sutherland, C., Irvine, A. D., & McLean, W. I. (2009). Filaggrin in the frontline: Role in skin barrier function and disease. Journal of Cell Science, 122(9), 1285–1294.PubMedPubMedCentralCrossRefGoogle Scholar
  207. 399.
    Saraiva, M., & O’garra, A. (2010). The regulation of IL-10 production by immune cells. Nature Reviews Immunology, 10(3), 170–181.PubMedCrossRefPubMedCentralGoogle Scholar
  208. 400.
    Savignac, M., Edir, A., Simon, M., & Hovnanian, A. (2011). Darier disease: A disease model of impaired calcium homeostasis in the skin. Biochimica et Biophysica Acta—Molecular Cell Research, 1813(5), 1111–1117.CrossRefGoogle Scholar
  209. 402.
    Schaerli, P., Willimann, K., Lang, A. B., Lipp, M., Loetscher, P., & Moser, B. (2000). CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. Journal of Experimental Medicine, 192(11), 1553–1562.PubMedCrossRefPubMedCentralGoogle Scholar
  210. 403.
    Scharschmidt, T. C., Man, M. Q., Hatano, Y., Crumrine, D., Gunathilake, R., Sundberg, J. P., et al. (2009). Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. Journal of Allergy and Clinical Immunology, 124(3), 496–506.PubMedCrossRefPubMedCentralGoogle Scholar
  211. 406.
    Schmitt, E., Klein, M., & Bopp, T. (2014). Th9 cells, new players in adaptive immunity. Trends in Immunology, 35(2), 61–68.PubMedCrossRefPubMedCentralGoogle Scholar
  212. 407.
    Schoepe, S., Schäcke, H., May, E., & Asadullah, K. (2006). Glucocorticoid therapy-induced skin atrophy. Experimental Dermatology, 15(6), 406–420.PubMedCrossRefPubMedCentralGoogle Scholar
  213. 408.
    Schrag, S. J., Peña, C., Fernández, J., Sánchez, J., Gómez, V., Pérez, E., et al. (2001). Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: A randomized trial. JAMA, 286(1), 49–56.PubMedCrossRefPubMedCentralGoogle Scholar
  214. 414.
    Sharlow, E. R., Paine, C. S., Babiarz, L., Eisinger, M., Shapiro, S., & Seiberg, M. (2000). The protease-activated receptor-2 upregulates keratinocyte phagocytosis. Journal of Cell Science, 113(17), 3093–3101.PubMedPubMedCentralGoogle Scholar
  215. 415.
    Shih, C., Padhy, L. C., Murray, M., & Weinberg, R. A. (1981). Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature, 290, 261–264.PubMedCrossRefPubMedCentralGoogle Scholar
  216. 416.
    Shih, C., & Weinberg, R. A. (1982). Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell, 29(1), 161–169.PubMedCrossRefPubMedCentralGoogle Scholar
  217. 418.
    Sidbury, R., Davis, D. M., Cohen, D. E., Cordoro, K. M., Berger, T. G., Bergman, J. N., et al. (2014). Guidelines of care for the management of atopic dermatitis: Section 3. Management and treatment with phototherapy and systemic agents. Journal of the American Academy of Dermatology, 71(2), 327–349.PubMedPubMedCentralCrossRefGoogle Scholar
  218. 420.
    Simpson, E. L., Chalmers, J. R., Hanifin, J. M., Thomas, K. S., Cork, M. J., McLean, W. I., et al. (2014). Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. Journal of Allergy and Clinical Immunology, 134(4), 818–823.PubMedCrossRefPubMedCentralGoogle Scholar
  219. 423.
    Sotiropoulou, G., & Pampalakis, G. (2010). Kallikrein-related peptidases: Bridges between immune functions and extracellular matrix degradation. Biological Chemistry, 391(4), 321–331.PubMedCrossRefPubMedCentralGoogle Scholar
  220. 424.
    Soto, A. M., & Sonnenschein, C. (2004). The somatic mutation theory of cancer: Growing problems with the paradigm?. Bioessays, 26(10), 1097–1107.PubMedCrossRefPubMedCentralGoogle Scholar
  221. 427.
    Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M. C., Di Giacomo, V., et al. (2013). Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell, 155(5), 1119–1130.PubMedCrossRefPubMedCentralGoogle Scholar
  222. 428.
    Stratton, M. R., Campbell, P. J., & Futreal, P. A. (2009). The cancer genome. Nature, 458(7239), 719–724.PubMedPubMedCentralCrossRefGoogle Scholar
  223. 430.
    Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., et al. (2005). Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences, 102(43), 15545–15550.CrossRefGoogle Scholar
  224. 431.
    Sugiura, A., Nomura, T., Mizuno, A., & Imokawa, G. (2014). Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: An abnormal permeability barrier homeostasis with defective processing to generate ceramide. Archives of Dermatological Research, 306(5), 427–440.PubMedCrossRefPubMedCentralGoogle Scholar
  225. 436.
    Taïeb, A., Seneschal, J., & Mossalayi, M. D. (2012). Biologics in atopic dermatitis. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 10(3), 174–178.PubMedPubMedCentralGoogle Scholar
  226. 437.
    Takai, T., & Ikeda, S. (2011). Barrier dysfunction caused by environmental proteases in the pathogenesis of allergic diseases. Allergology International, 60(1), 25–35.PubMedCrossRefPubMedCentralGoogle Scholar
  227. 438.
    Tanaka, G., Christodoulides, P., Domínguez-Hüttinger, E., Aihara, K., & Tanaka, R. J. (2018). Bifurcation analysis of a mathematical model of atopic dermatitis to determine patient-specific effects of treatments on dynamic phenotypes. Journal of Theoretical Biology, 448, 66–79.PubMedCrossRefPubMedCentralGoogle Scholar
  228. 439.
    Tanaka, R. J., Ono, M., & Harrington, H. A. (2011). Skin barrier homeostasis in atopic dermatitis: Feedback regulation of kallikrein activity. PloS One, 6(5), e19895.PubMedPubMedCentralCrossRefGoogle Scholar
  229. 441.
    Tang, T. S., Bieber, T., & Williams, H. C. (2014). Are the concepts of induction of remission and treatment of subclinical inflammation in atopic dermatitis clinically useful?. Journal of Allergy and Clinical Immunology, 133(6), 1615–1625.PubMedCrossRefPubMedCentralGoogle Scholar
  230. 444.
    Terui, T., Hirao, T., Sato, Y., Uesugi, T., Honda, M., Iguchi, M., et al. (1998). An increased ratio of interleukin-1 receptor antagonist to interleukin-1α in inflammatory skin diseases. Experimental Dermatology, 7(6), 327–334.PubMedCrossRefPubMedCentralGoogle Scholar
  231. 448.
    Thyssen, J. P., & Kezic, S. (2014). Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis. Journal of Allergy and Clinical Immunology, 134(4), 792–799.PubMedCrossRefPubMedCentralGoogle Scholar
  232. 456.
    Tu, C. L., Crumrine, D. A., Man, M. Q., Chang, W., Elalieh, H., You, M., et al. (2012). Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. Journal of Investigative Dermatology, 132(10), 2350–2359.PubMedCrossRefPubMedCentralGoogle Scholar
  233. 463.
    Van Kruijsdijk, R. C., van der Wall, E., & Visseren, F. L. (2009). Obesity and cancer: The role of dysfunctional adipose tissue. Cancer Epidemiology and Prevention Biomarkers, 18(10), 2569–2578.CrossRefGoogle Scholar
  234. 467.
    Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006). TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity, 24(2), 179–189.CrossRefPubMedGoogle Scholar
  235. 468.
    Villarreal, C., Padilla-Longoria, P., & Álvarez-Buylla, E. R. (2012). General theory of genotype to phenotype mapping: Derivation of epigenetic landscapes from N-node complex gene regulatory networks. Physical Review Letters, 109(11), 118102.PubMedCrossRefPubMedCentralGoogle Scholar
  236. 469.
    Vinuesa, C. G., Fagarasan, S., & Dong, C. (2013). New territory for T follicular helper cells. Immunity, 39(3), 417–420.PubMedCrossRefPubMedCentralGoogle Scholar
  237. 470.
    Virchow, R. (1858). Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre: zwanzig Vorlesungen, gehalten während der Monate Februar, März und April 1858 im pathologischen Institute zu Berlin. Hirschwald.Google Scholar
  238. 471.
    Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., et al. (1988). Genetic alterations during colorectal-tumor development. New England Journal of Medicine, 319(9), 525–532.PubMedCrossRefPubMedCentralGoogle Scholar
  239. 474.
    Wadonda-Kabondo, N., Sterne, J. A. C., Golding, J., Kennedy, C. T. C., Archer, C. B., Dunnill, M. G. S., et al. (2003). A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0–42 months. British Journal of Dermatology, 149(5), 1023–1028. Epidemiology and Health Services Research.Google Scholar
  240. 476.
    Wang, G., Yuan, R., Zhu, X., & Ao, P. (2018). Endogenous molecular-cellular network cancer theory: A systems biology approach. In M. Bizzarri (Ed.), Systems biology. Methods in molecular biology (Vol. 1702). New York: Humana Press.Google Scholar
  241. 477.
    Wang, G., Zhu, X., Gu, J., & Ao, P. (2014). Quantitative implementation of the endogenous molecular–cellular network hypothesis in hepatocellular carcinoma. Interface Focus, 4(3), 20130064.PubMedPubMedCentralCrossRefGoogle Scholar
  242. 480.
    Warrell, M. J. (2011). Intradermal rabies vaccination: The evolution and future of pre-and post-exposure prophylaxis. In Intradermal immunization (pp. 139–157). Berlin: Springer.CrossRefGoogle Scholar
  243. 481.
    Watson, I. R., Takahashi, K., Futreal, P. A., & Chin, L. (2013). Emerging patterns of somatic mutations in cancer. Nature Reviews Genetics, 14(10), 703–718.PubMedPubMedCentralCrossRefGoogle Scholar
  244. 484.
    Weinberg, R. A. (1991). Tumor suppressor genes. Science, 254(5035), 1138–1146.PubMedCrossRefPubMedCentralGoogle Scholar
  245. 485.
    Weiner, H. L., da Cunha, A. P., Quintana, F., & Wu, H. (2011). Oral tolerance. Immunological Reviews, 241(1), 241–259.PubMedPubMedCentralCrossRefGoogle Scholar
  246. 486.
    Weinstein, J. N., Collisson, E. A., Mills, G. B., Shaw, K. R. M., Ozenberger, B. A., Ellrott, K., et al. (2013). The cancer genome atlas pan-cancer analysis project. Nature Genetics, 45(10), 1113–1120.PubMedPubMedCentralCrossRefGoogle Scholar
  247. 490.
    Willhauck, M. J., Mirancea, N., Vosseler, S., Pavesio, A., Boukamp, P., Mueller, M. M., et al. (2007). Reversion of tumor phenotype in surface transplants of skin SCC cells by scaffold-induced stroma modulation. Carcinogenesis, 28(3), 595–610.PubMedCrossRefPubMedCentralGoogle Scholar
  248. 492.
    Wills-Karp, M., Santeliz, J., & Karp, C. L. (2001). The germless theory of allergic disease: Revisiting the hygiene hypothesis. Nature Reviews Immunology, 1(1), 69–75.PubMedCrossRefPubMedCentralGoogle Scholar
  249. 496.
    Wuensche, A. (1998, January). Genomic regulation modeled as a network with basins of attraction. In Pacific Symposium on Biocomputing (Vol. 3, pp. 89–102).Google Scholar
  250. 498.
    Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., et al. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation, 112(12), 1821.PubMedPubMedCentralCrossRefGoogle Scholar
  251. 499.
    Xu, J., Lamouille, S., & Derynck, R. (2009). TGF-β-induced epithelial to mesenchymal transition. Cell Research, 19(2), 156–172.PubMedPubMedCentralCrossRefGoogle Scholar
  252. 500.
    Xu, L., Kitani, A., Fuss, I., & Strober, W. (2007). Cutting edge: Regulatory T cells induce CD4+ CD25- Foxp3-T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-β. The Journal of Immunology, 178(11), 6725–6729.PubMedCrossRefPubMedCentralGoogle Scholar
  253. 501.
    Yaffe, M. B. (2013). The scientific drunk and the lamppost: Massive sequencing efforts in cancer discovery and treatment. Science Signaling, 6(269), pe13.Google Scholar
  254. 502.
    Yamane, H., Zhu, J., & Paul, W. E. (2005). Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment. Journal of Experimental Medicine, 202(6), 793–804.PubMedCrossRefPubMedCentralGoogle Scholar
  255. 503.
    Yates, A., Bergmann, C., Van Hemmen, J. L., Stark, J., & Callard, R. (2000). Cytokine-modulated regulation of helper T cell populations. Journal of Theoretical Biology, 206(4), 539–560.PubMedCrossRefPubMedCentralGoogle Scholar
  256. 504.
    Ye, X., & Weinberg, R. A. (2015). Epithelial–mesenchymal plasticity: A central regulator of cancer progression. Trends in Cell Biology, 25(11), 675–686.PubMedPubMedCentralCrossRefGoogle Scholar
  257. 506.
    Yoshimura, A., Naka, T., & Kubo, M. (2007). SOCS proteins, cytokine signalling and immune regulation. Nature Reviews Immunology, 7(6), 454–465.PubMedCrossRefPubMedCentralGoogle Scholar
  258. 507.
    Yoshimura, A., Suzuki, M., Sakaguchi, R., Hanada, T., & Yasukawa, H. (2012). SOCS, inflammation, and autoimmunity. Frontiers in Immunology, 3, 20.PubMedPubMedCentralCrossRefGoogle Scholar
  259. 510.
    Yuan, R., Zhu, X., Radich, J. P., & Ao, P. (2016). From molecular interaction to acute promyelocytic leukemia: Calculating leukemogenesis and remission from endogenous molecular-cellular network. Scientific Reports, 6, 24307.PubMedPubMedCentralCrossRefGoogle Scholar
  260. 514.
    Zhang, Y. (2013). Cancer embryonic stem cell-like attractors alongside deficiency of regulatory restraints of cell-division and cell-cycle. Journal of Genetic Syndromes and Gene Therapy, 4(130), 2.Google Scholar
  261. 515.
    Zhang, Z., Clarke, T. B., & Weiser, J. N. (2009). Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. The Journal of Clinical Investigation, 119(7), 1899.PubMedPubMedCentralGoogle Scholar
  262. 517.
    Zheng, T., Yu, J., Oh, M. H., & Zhu, Z. (2011). The atopic march: Progression from atopic dermatitis to allergic rhinitis and asthma. Allergy, Asthma & Immunology Research, 3(2), 67–73.CrossRefGoogle Scholar
  263. 518.
    Zhou, J. X., & Huang, S. (2011). Understanding gene circuits at cell-fate branch points for rational cell reprogramming. Trends in Genetics, 27(2), 55–62.PubMedCrossRefPubMedCentralGoogle Scholar
  264. 521.
    Zhu, J., Yamane, H., & Paul, W. E. (2009). Differentiation of effector CD4 T cell populations. Annual Review of Immunology, 28, 445–489.CrossRefGoogle Scholar
  265. 522.
    Zhu, X., Yuan, R., Hood, L., & Ao, P. (2015). Endogenous molecular-cellular hierarchical modeling of prostate carcinogenesis uncovers robust structure. Progress in Biophysics and Molecular Biology, 117(1), 30–42.PubMedCrossRefPubMedCentralGoogle Scholar
  266. 523.
    Zitvogel, L., Pietrocola, F., & Kroemer, G. (2017). Nutrition, inflammation and cancer. Nature Immunology, 18(8), 843–850.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • María Elena Álvarez-Buylla Roces
    • 1
  • Juan Carlos Martínez-García
    • 2
  • José Dávila-Velderrain
    • 3
  • Elisa Domínguez-Hüttinger
    • 4
  • Mariana Esther Martínez-Sánchez
    • 1
  1. 1.Ciudad Universitaria, UNAM, Instituto de EcologíaCiudad de MéxicoMexico
  2. 2.Departamento de Control AutomáticoCINVESTAVCiudad de MéxicoMexico
  3. 3.CSIL, Massachusetts Institute of TechnologyCambridgeUSA
  4. 4.Centro de Ciencias Matemáticas, UNAMMoreliaMéxico

Personalised recommendations