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Sessile Innate Immune Cells

  • Walter Gottlieb Land
Chapter

Abstract

In this chapter, sessile cells of the innate immune system are briefly introduced. Defined as cells equipped with diverse pattern recognition molecules capable of detecting MAMPs and DAMPs, they encompass cells such as epithelial cells, fibroblasts, vascular cells, chondrocytes, osteoblasts, and adipocytes. Located at the body surfaces, epithelial cells represent the first line of innate immune defense against invading microbial pathogens. They are significant contributors to innate mucosal immunity and generate various antimicrobial defense mechanisms. Also, epithelial cells critically contribute to tissue repair via the phenomenon of re-epithelialization. Fibroblasts operate as classical sentinel cells of the innate immune system dedicated to responding to MAMPs and DAMPs emitted upon any tissue injury. Typically, fibroblasts synthesize most of the extracellular matrix of connective tissues, thereby playing a crucial role in tissue repair processes. Vascular cells of the innate immune system represent an evolutionarily developed first-line defense against any inciting insult hitting the vessel walls from the luminal side including bacteria, viruses, microbial toxins, and chemical noxa such as nicotine. Upon such insults and following recognition of MAMPs and DAMPs, vascular cells react with an innate immune response to create an acute inflammatory milieu in the vessel wall aimed at curing the vascular injury concerned. Chondrocytes, osteoblasts, and osteoclasts represent other vital cells of the skeletal system acting as cells of the innate immune system in its wider sense. These cells mediate injury-promoted DAMP-induced inflammatory and regenerative processes specific for the skeletal systems. Finally, adipocytes are regarded as highly active cells of the innate immune system. As white, brown, and beige adipocytes, they operate as a dynamic metabolic organ that can secrete certain bioactive molecules which have endocrine, paracrine, and autocrine actions.

References

  1. 1.
    Uehara A, Fujimoto Y, Fukase K, Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol. 2007;44:3100–11. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17403538.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Shaykhiev R, Behr J, Bals R. Microbial patterns signaling via Toll-like receptors 2 and 5 contribute to epithelial repair, growth and survival. PLoS One. 2008;3:e1393. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18167552.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Strbo N, Yin N, Stojadinovic O. Innate and adaptive immune responses in wound epithelialization. Adv Wound Care. 2014;3:492–501. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25032069.CrossRefGoogle Scholar
  4. 4.
    Miller LS, Modlin RL. Toll-like receptors in the skin. Semin Immunopathol. 2007;29:15–26. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17621951.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Tervaniemi MH, Katayama S, Skoog T, Siitonen HA, Vuola J, Nuutila K, et al. NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis. Sci Rep. 2016;6:22745. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26976200.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Chowdhari S, Saini N. Gene expression profiling reveals the role of RIG1 like receptor signaling in p53 dependent apoptosis induced by PUVA in keratinocytes. Cell Signal. 2016;28:25–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26518362.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Reinholz M, Kawakami Y, Salzer S, Kreuter A, Dombrowski Y, Koglin S, et al. HPV16 activates the AIM2 inflammasome in keratinocytes. Arch Dermatol Res. 2013;305:723–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23764897.CrossRefGoogle Scholar
  8. 8.
    Mishra PJ, Mishra PJ, Banerjee D. Keratinocyte induced differentiation of mesenchymal stem cells into dermal myofibroblasts: a role in effective wound healing. Int J Transl Sci. 2016;2016:5–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27294075.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Bhatia A, O’Brien K, Chen M, Woodley DT, Li W. Keratinocyte-secreted heat shock protein-90alpha: leading wound reepithelialization and closure. Adv Wound Care. 2016;5:176–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27076995.CrossRefGoogle Scholar
  10. 10.
    de Koning HD, Simon A, Zeeuwen PLJM, Schalkwijk J. Pattern recognition receptors in immune disorders affecting the skin. J Innate Immun. 2012;4:225–40. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22398307.CrossRefGoogle Scholar
  11. 11.
    Dale BA. Periodontal epithelium: a newly recognized role in health and disease. Periodontol 2000. 2002;30:70–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12236897.CrossRefGoogle Scholar
  12. 12.
    Hans M, Madaan Hans V. Epithelial antimicrobial peptides: guardian of the oral cavity. Int J Pept. 2014;2014:1–13. Available from: http://www.hindawi.com/journals/ijpep/2014/370297/.CrossRefGoogle Scholar
  13. 13.
    Diamond G, Beckloff N, Ryan LK. Host defense peptides in the oral cavity and the lung: similarities and differences. J Dent Res. 2008;87:915–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18809744.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Crump KE, Sahingur SE. Microbial nucleic acid sensing in oral and systemic diseases. J Dent Res. 2016;95:17–25. Available from: http://jdr.sagepub.com/cgi/doi/10.1177/0022034515609062.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Prates TP, Taira TM, Holanda MC, Bignardi LA, Salvador SL, Zamboni DS, et al. NOD2 contributes to porphyromonas gingivalis-induced bone resorption. J Dent Res. 2014;93:1155–62. Available from: http://jdr.sagepub.com/cgi/doi/10.1177/0022034514551770.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Bui FQ, Johnson L, Roberts J, Hung S-C, Lee J, Atanasova KR, et al. Fusobacterium nucleatum infection of gingival epithelial cells leads to NLRP3 inflammasome-dependent secretion of IL-1β and the danger signals ASC and HMGB1. Cell Microbiol. 2016;18:970–81. Available from: http://doi.wiley.com/10.1111/cmi.12560.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Silva N, Abusleme L, Bravo D, Dutzan N, Garcia-Sesnich J, Vernal R, et al. Host response mechanisms in periodontal diseases. J Appl Oral Sci. 2015;23:329–55. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-77572015000300329&lng=en&nrm=iso&tlng=en.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP. Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol. 2004;31:358–64. Available from: http://www.atsjournals.org/doi/abs/10.1165/rcmb.2003-0388OC.CrossRefGoogle Scholar
  19. 19.
    Hauber H-P, Tulic MK, Tsicopoulos A, Wallaert B, Olivenstein R, Daigneault P, et al. Toll-like receptors 4 and 2 expression in the bronchial mucosa of patients with cystic fibrosis. Can Respir J. 2005;12:13–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15776129.CrossRefGoogle Scholar
  20. 20.
    Jiang D, Liang J, Li Y, Noble PW. The role of toll-like receptors in non-infectious lung injury. Cell Res. 2006;16:693–701. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16894359.CrossRefGoogle Scholar
  21. 21.
    Lafferty EI, Qureshi ST, Schnare M. The role of toll-like receptors in acute and chronic lung inflammation. J Inflamm. 2010;7:57. Available from: http://journal-inflammation.biomedcentral.com/articles/10.1186/1476-9255-7-57.CrossRefGoogle Scholar
  22. 22.
    Hippenstiel S, Opitz B, Schmeck B, Suttorp N. Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction. Respir Res. 2006;7:97. Available from: http://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-7-97.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Peeters PM, Perkins TN, Wouters EFM, Mossman BT, Reynaert NL. Silica induces NLRP3 inflammasome activation in human lung epithelial cells. Part Fibre Toxicol. 2013;10:3. Available from: http://particleandfibretoxicology.biomedcentral.com/articles/10.1186/1743-8977-10-3.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Gao W, Li L, Wang Y, Zhang S, Adcock IM, Barnes PJ, et al. Bronchial epithelial cells: the key effector cells in the pathogenesis of chronic obstructive pulmonary disease? Respirology. 2015;20:722–9. Available from: http://doi.wiley.com/10.1111/resp.12542.PubMedCentralCrossRefGoogle Scholar
  25. 25.
    Radman M, Golshiri A, Shamsizadeh A, Zainodini N, Bagheri V, Arababadi MK, et al. Toll-like receptor 4 plays significant roles during allergic rhinitis. Allergol Immunopathol (Madr). 2015;43:416–20. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0301054614001001.CrossRefGoogle Scholar
  26. 26.
    Papaioannou AI, Spathis A, Kostikas K, Karakitsos P, Papiris S, Rossios C. The role of endosomal toll-like receptors in asthma. Eur J Pharmacol. 2017;808:14. http://linkinghub.elsevier.com/retrieve/pii/S0014299916306203 CrossRefGoogle Scholar
  27. 27.
    Lallès J-P. Microbiota-host interplay at the gut epithelial level, health and nutrition. J Anim Sci Biotechnol. 2016;7:66. Available from: http://jasbsci.biomedcentral.com/articles/10.1186/s40104-016-0123-7.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Wang M, Monaco MH, Donovan SM. Impact of early gut microbiota on immune and metabolic development and function. Semin Fetal Neonatal Med. 2016;21:380–7. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1744165X1630004X.CrossRefGoogle Scholar
  29. 29.
    Crosnier C, Stamataki D, Lewis J. Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat Rev Genet. 2006;7:349–59. Available from: http://www.nature.com/doifinder/10.1038/nrg1840.CrossRefGoogle Scholar
  30. 30.
    Barker N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol. 2013;15:19–33. Available from: http://www.nature.com/doifinder/10.1038/nrm3721.CrossRefGoogle Scholar
  31. 31.
    Mabbott NA, Donaldson DS, Ohno H, Williams IR, Mahajan A. Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium. Mucosal Immunol. 2013;6:666–77. Available from: http://www.nature.com/doifinder/10.1038/mi.2013.30.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Wells JM, Rossi O, Meijerink M, van Baarlen P. Epithelial crosstalk at the microbiota-mucosal interface. Proc Natl Acad Sci. 2011;108:4607–14. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.1000092107.CrossRefGoogle Scholar
  33. 33.
    Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014;14:141–53. Available from: http://www.nature.com/doifinder/10.1038/nri3608.CrossRefGoogle Scholar
  34. 34.
    Yu S, Gao N. Compartmentalizing intestinal epithelial cell toll-like receptors for immune surveillance. Cell Mol Life Sci. 2015;72:3343–53. Available from: http://link.springer.com/10.1007/s00018-015-1931-1.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Parlato M, Yeretssian G. NOD-like receptors in intestinal homeostasis and epithelial tissue repair. Int J Mol Sci. 2014;15:9594–627. Available from: http://www.mdpi.com/1422-0067/15/6/9594/.PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Sellin ME, Maslowski KM, Maloy KJ, Hardt W-D. Inflammasomes of the intestinal epithelium. Trends Immunol. 2015;36:442–50. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1471490615001465.CrossRefGoogle Scholar
  37. 37.
    Kawaguchi S, Ishiguro Y, Imaizumi T, Mori F, Matsumiya T, Yoshida H, et al. Retinoic acid-inducible gene-I is constitutively expressed and involved in IFN-γ-stimulated CXCL9–11 production in intestinal epithelial cells. Immunol Lett. 2009;123:9–13. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0165247809000091.CrossRefGoogle Scholar
  38. 38.
    Vanhove W, Peeters PM, Staelens D, Schraenen A, Van der Goten J, Cleynen I, et al. Strong upregulation of AIM2 and IFI16 inflammasomes in the mucosa of patients with active inflammatory bowel disease. Inflamm Bowel Dis. 2015;21:2673–82. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00054725-201511000-00023.CrossRefGoogle Scholar
  39. 39.
    Elia PP, Tolentino YFM, Bernardazzi C, de Souza HSP. The role of innate immunity receptors in the pathogenesis of inflammatory bowel disease. Mediators Inflamm. 2015;2015:1–10. Available from: http://www.hindawi.com/journals/mi/2015/936193/.CrossRefGoogle Scholar
  40. 40.
    Sidiq T, Yoshihama S, Downs I, Kobayashi KS. Nod2: a critical regulator of ileal microbiota and Crohn’s disease. Front Immunol. 2016;7:367. Available from: http://journal.frontiersin.org/Article/10.3389/fimmu.2016.00367/abstract.PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature. 2016;535:65–74. Available from: http://www.nature.com/doifinder/10.1038/nature18847.CrossRefGoogle Scholar
  42. 42.
    Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, et al. Fecal microbiota, fecal metabolome, and colorectal cancer interrelations. PLoS One. 2016;11:e0152126. Available from: http://dx.plos.org/10.1371/journal.pone.0152126.PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    O’Hara SP, Tabibian JH, Splinter PL, LaRusso NF. The dynamic biliary epithelia: molecules, pathways, and disease. J Hepatol. 2013;58:575–82. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0168827812008100.CrossRefGoogle Scholar
  44. 44.
    Strazzabosco M, Fabris L. Development of the bile ducts: essentials for the clinical hepatologist. J Hepatol. 2012;56:1159–70. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0168827812000372.PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Yang L, Seki E. Toll-like receptors in liver fibrosis: cellular crosstalk and mechanisms. Front Physiol. 2012;3:138. Available from: http://journal.frontiersin.org/article/10.3389/fphys.2012.00138/abstract.PubMedCentralPubMedGoogle Scholar
  46. 46.
    Harada K, Nakanuma Y. Cholangiopathy with respect to biliary innate immunity. Int J Hepatol. 2012;2012:1–10. Available from: http://www.hindawi.com/journals/ijh/2012/793569/.CrossRefGoogle Scholar
  47. 47.
    Al-Awqati Q, Schwartz GJ. A fork in the road of cell differentiation in the kidney tubule. J Clin Invest. 2004;113:1528–30. Available from: http://www.jci.org/articles/view/22029.PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Chowdhury P, Sacks SH, Sheerin NS. Toll-like receptors TLR2 and TLR4 initiate the innate immune response of the renal tubular epithelium to bacterial products. Clin Exp Immunol. 2006;145:346–56. Available from: http://doi.wiley.com/10.1111/j.1365-2249.2006.03116.x.PubMedCentralCrossRefPubMedGoogle Scholar
  49. 49.
    Wolfs TGAM, Buurman WA, van Schadewijk A, de Vries B, Daemen MARC, Hiemstra PS, et al. In vivo expression of Toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol. 2002;168:1286–93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11801667.CrossRefGoogle Scholar
  50. 50.
    Tsuboi N, Yoshikai Y, Matsuo S, Kikuchi T, Iwami K-I, Nagai Y, et al. Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. J Immunol. 2002;169:2026–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12165529.CrossRefGoogle Scholar
  51. 51.
    Samuelsson P, Hang L, Wullt B, Irjala H, Svanborg C. Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa. Infect Immun. 2004;72:3179–86. Available from: http://iai.asm.org/cgi/doi/10.1128/IAI.72.6.3179-3186.2004.PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Fu Y, Xie C, Chen J, Zhu J, Zhou H, Thomas J, et al. Innate stimuli accentuate end-organ damage by nephrotoxic antibodies via Fc receptor and TLR stimulation and IL-1/TNF-alpha production. J Immunol. 2006;176:632–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16365459.CrossRefGoogle Scholar
  53. 53.
    Kim BS, Lim SW, Li C, Kim JS, Sun BK, Ahn KO, et al. Ischemia-reperfusion injury activates innate immunity in rat kidneys. Transplantation. 2005;79:1370–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15912106.CrossRefGoogle Scholar
  54. 54.
    Ben Mkaddem S, Chassin C, Vandewalle A. Contribution of renal tubule epithelial cells in the innate immune response during renal bacterial infections and ischemia-reperfusion injury. Chang Gung Med J. 2010;33:225–40. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20584500.PubMedGoogle Scholar
  55. 55.
    Heutinck KM, Rowshani AT, Kassies J, Claessen N, van Donselaar-van der Pant KAMI, Bemelman FJ, et al. Viral double-stranded RNA sensors induce antiviral, pro-inflammatory, and pro-apoptotic responses in human renal tubular epithelial cells. Kidney Int. 2012;82:664–75. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0085253815556172.CrossRefGoogle Scholar
  56. 56.
    Mulay SR, Kumar SV, Lech M, Desai J, Anders H-J. How kidney cell death induces renal necroinflammation. Semin Nephrol. 2016;36:162–73. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0270929516000243.CrossRefGoogle Scholar
  57. 57.
    Iorember FM, Vehaskari VM. Uromodulin: old friend with new roles in health and disease. Pediatr Nephrol. 2014;29:1151–8. Available from: http://link.springer.com/10.1007/s00467-013-2563-z.CrossRefGoogle Scholar
  58. 58.
    Schaefer TM, Desouza K, Fahey JV, Beagley KW, Wira CR. Toll-like receptor (TLR) expression and TLR-mediated cytokine/chemokine production by human uterine epithelial cells. Immunology. 2004;112:428–36. Available from: http://doi.wiley.com/10.1111/j.1365-2567.2004.01898.x.PubMedCentralCrossRefPubMedGoogle Scholar
  59. 59.
    Lamont R, Sobel J, Akins R, Hassan S, Chaiworapongsa T, Kusanovic J, et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG An Int J Obstet Gynaecol. 2011;118:533–49. Available from: http://doi.wiley.com/10.1111/j.1471-0528.2010.02840.x.CrossRefGoogle Scholar
  60. 60.
    Quayle AJ. The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells. J Reprod Immunol. 2002;57:61–79. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12385834.CrossRefGoogle Scholar
  61. 61.
    Wira CR, Fahey JV, Sentman CL, Pioli PA, Shen L. Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol Rev. 2005;206:306–35. Available from: http://doi.wiley.com/10.1111/j.0105-2896.2005.00287.x.CrossRefGoogle Scholar
  62. 62.
    Andersen JM, Al-Khairy D, Ingalls RR. Innate immunity at the mucosal surface: role of toll-like receptor 3 and toll-like receptor 9 in cervical epithelial cell responses to microbial pathogens. Biol Reprod. 2006;74:824–31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16421230.CrossRefGoogle Scholar
  63. 63.
    Fichorova RN, Cronin AO, Lien E, Anderson DJ, Ingalls RR. Response to Neisseria gonorrhoeae by cervicovaginal epithelial cells occurs in the absence of toll-like receptor 4-mediated signaling. J Immunol. 2002;168:2424–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11859134.CrossRefGoogle Scholar
  64. 64.
    Young SL, Lyddon TD, Jorgenson RL, Misfeldt ML. Expression of toll-like receptors in human endometrial epithelial cells and cell lines. Am J Reprod Immunol. 2004;52:67–73. Available from: http://doi.wiley.com/10.1111/j.1600-0897.2004.00189.x.PubMedCentralCrossRefPubMedGoogle Scholar
  65. 65.
    Sathe A, Reddy KVR. TLR9 and RIG-I signaling in human endocervical epithelial cells modulates inflammatory responses of macrophages and dendritic cells in vitro. Kumar A, editor. PLoS One. 2014;9:e83882. Available from: http://dx.plos.org/10.1371/journal.pone.0083882.PubMedCentralCrossRefPubMedGoogle Scholar
  66. 66.
    Tang S, Moyes D, Richardson J, Blagojevic M, Naglik J. Epithelial discrimination of commensal and pathogenic Candida albicans. Oral Dis. 2016;22:114–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26843519.CrossRefGoogle Scholar
  67. 67.
    Smith RS, Smith TJ, Blieden TM, Phipps RP. Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of inflammation. Am J Pathol. 1997;151:317–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9250144.PubMedCentralPubMedGoogle Scholar
  68. 68.
    Turner NA. Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs). J Mol Cell Cardiol. 2016;94:189–200. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26542796.CrossRefGoogle Scholar
  69. 69.
    Chang Y, Li H, Guo Z. Mesenchymal stem cell-like properties in fibroblasts. Cell Physiol Biochem. 2014;34:703–14. Available from: http://www.karger.com?doi=10.1159/000363035.CrossRefGoogle Scholar
  70. 70.
    Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214:199–210.  https://doi.org/10.1002/path.2277.CrossRefPubMedCentralPubMedGoogle Scholar
  71. 71.
    Lee K, Nelson CM. New insights into the regulation of epithelial–mesenchymal transition and tissue fibrosis. Int Rev Cell Mol Biol. 2012;294:171–221. Available from: http://linkinghub.elsevier.com/retrieve/pii/B9780123943057000045.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Hashimoto N, Phan SH, Imaizumi K, Matsuo M, Nakashima H, Kawabe T, et al. Endothelial–mesenchymal transition in bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 2010;43:161–72. Available from: http://www.atsjournals.org/doi/abs/10.1165/rcmb.2009-0031OC.CrossRefGoogle Scholar
  73. 73.
    Medici D. Endothelial-mesenchymal transition in regenerative medicine. Stem Cells Int. 2016;2016:1–7. Available from: http://www.hindawi.com/journals/sci/2016/6962801/.Google Scholar
  74. 74.
    Ebihara Y, Masuya M, LaRue AC, Fleming PA, Visconti RP, Minamiguchi H, et al. Hematopoietic origins of fibroblasts: II. In vitro studies of fibroblasts, CFU-F, and fibrocytes. Exp Hematol. 2006;34:219–29. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0301472X05005023.CrossRefGoogle Scholar
  75. 75.
    Sundberg C, Ivarsson M, Gerdin B, Rubin K. Pericytes as collagen-producing cells in excessive dermal scarring. Lab Invest. 1996;74:452–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8780163.PubMedGoogle Scholar
  76. 76.
    Artlett CM, Thacker JD. Molecular activation of the NLRP3 inflammasome in fibrosis: common threads linking divergent fibrogenic diseases. Antioxid Redox Signal. 2015;22:1162–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25329971.CrossRefGoogle Scholar
  77. 77.
    Kostyuk SV, Tabakov VJ, Chestkov VV, Konkova MS, Glebova KV, Baydakova GV, et al. Oxidized DNA induces an adaptive response in human fibroblasts. Mutat Res Mol Mech Mutagen. 2013;747–748:6–18. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0027510713000481.CrossRefGoogle Scholar
  78. 78.
    Portou MJJ, Baker D, Abraham D, Tsui J. The innate immune system, toll-like receptors and dermal wound healing: a review. Vascul Pharmacol. 2015;71:31–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25869514.CrossRefGoogle Scholar
  79. 79.
    Uehara A, Takada H. Functional TLRs and NODs in human gingival fibroblasts. J Dent Res. 2007;86:249–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17314257.CrossRefGoogle Scholar
  80. 80.
    He Z-W, Qin Y-H, Wang Z-W, Chen Y, Shen Q, Dai S-M. HMGB1 acts in synergy with lipopolysaccharide in activating rheumatoid synovial fibroblasts via p38 MAPK and NF- κ B signaling pathways. Mediators Inflamm. 2013;2013:1–10. Available from: http://www.hindawi.com/journals/mi/2013/596716/.CrossRefGoogle Scholar
  81. 81.
    Homer RJ, Elias JA, Lee CG, Herzog E. Modern concepts on the role of inflammation in pulmonary fibrosis. Arch Pathol Lab Med. 2011;135:780–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21631273.PubMedGoogle Scholar
  82. 82.
    Aird WC. Spatial and temporal dynamics of the endothelium. J Thromb Haemost. 2005;3:1392–406. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15892866.CrossRefGoogle Scholar
  83. 83.
    Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, et al. An estimation of the number of cells in the human body. Ann Hum Biol. 2013;40:463–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23829164.CrossRefGoogle Scholar
  84. 84.
    Khakpour S, Wilhelmsen K, Hellman J. Vascular endothelial cell Toll-like receptor pathways in sepsis. Innate Immun. 2015;21:827–46. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26403174.CrossRefGoogle Scholar
  85. 85.
    Sturtzel C. Endothelial cells. Adv Exp Med Biol. 2017;1003:71–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28667554.CrossRefGoogle Scholar
  86. 86.
    Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7:678–89. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17717539.CrossRefGoogle Scholar
  87. 87.
    Hickey MJ, Kubes P. Intravascular immunity: the host-pathogen encounter in blood vessels. Nat Rev Immunol. 2009;9:364–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19390567.CrossRefGoogle Scholar
  88. 88.
    Pryshchep O, Ma-Krupa W, Younge BR, Goronzy JJ, Weyand CM. Vessel-specific Toll-like receptor profiles in human medium and large arteries. Circulation. 2008;118:1276–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18765390.PubMedCentralCrossRefPubMedGoogle Scholar
  89. 89.
    Wu J, Meng Z, Jiang M, Zhang E, Trippler M, Broering R, et al. Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific. Immunology. 2010;129:363–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19922426.PubMedCentralCrossRefPubMedGoogle Scholar
  90. 90.
    Garrafa E, Imberti L, Tiberio G, Prandini A, Giulini SM, Caimi L. Heterogeneous expression of toll-like receptors in lymphatic endothelial cells derived from different tissues. Immunol Cell Biol. 2011;89:475–81. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20921966.CrossRefGoogle Scholar
  91. 91.
    El Kebir D, Damlaj A, Makhezer N, Filep JG. Toll-like receptor 9 signaling regulates tissue factor and tissue factor pathway inhibitor expression in human endothelial cells and coagulation in mice. Crit Care Med. 2015;43:e179–89. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25855902.PubMedCentralCrossRefPubMedGoogle Scholar
  92. 92.
    Stribos EGD, van Werkhoven MB, Poppelaars F, van Goor H, Olinga P, van Son WJ, et al. Renal expression of Toll-like receptor 2 and 4: dynamics in human allograft injury and comparison to rodents. Mol Immunol. 2015;64:82–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25465639.CrossRefGoogle Scholar
  93. 93.
    Martin-Rodriguez S, Caballo C, Gutierrez G, Vera M, Cruzado JM, Cases A, et al. TLR4 and NALP3 inflammasome in the development of endothelial dysfunction in uraemia. Eur J Clin Invest. 2015;45:160–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25496217.CrossRefGoogle Scholar
  94. 94.
    Gatheral T, Reed DM, Moreno L, Gough PJ, Votta BJ, Sehon CA, et al. A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses. PLoS One. 2012;7:e42386. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22870324.PubMedCentralCrossRefPubMedGoogle Scholar
  95. 95.
    Opitz B, Eitel J, Meixenberger K, Suttorp N. Role of Toll-like receptors, NOD-like receptors and RIG-I-like receptors in endothelial cells and systemic infections. Thromb Haemost. 2009;102:1103–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19967140.CrossRefGoogle Scholar
  96. 96.
    Nagyőszi P, Nyúl-Tóth Á, Fazakas C, Wilhelm I, Kozma M, Molnár J, et al. Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells. J Neurochem. 2015;135:551–64. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26083549.CrossRefGoogle Scholar
  97. 97.
    Chen Y, Pitzer AL, Li X, Li P-L, Wang L, Zhang Y. Instigation of endothelial Nlrp3 inflammasome by adipokine visfatin promotes inter-endothelial junction disruption: role of HMGB1. J Cell Mol Med. 2015;19:2715–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26293846.PubMedCentralCrossRefPubMedGoogle Scholar
  98. 98.
    Imaizumi T, Aratani S, Nakajima T, Carlson M, Matsumiya T, Tanji K, et al. Retinoic acid-inducible gene-I is induced in endothelial cells by LPS and regulates expression of COX-2. Biochem Biophys Res Commun. 2002;292:274–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11890704.CrossRefGoogle Scholar
  99. 99.
    Asdonk T, Motz I, Werner N, Coch C, Barchet W, Hartmann G, et al. Endothelial RIG-I activation impairs endothelial function. Biochem Biophys Res Commun. 2012;420:66–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22402283.CrossRefGoogle Scholar
  100. 100.
    Moser J, Heeringa P, Jongman RM, Zwiers PJ, Niemarkt AE, Yan R, et al. Intracellular RIG-I signaling regulates TLR4-independent endothelial inflammatory responses to endotoxin. J Immunol. 2016;196:4681–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27183587.CrossRefGoogle Scholar
  101. 101.
    Faure E, Equils O, Sieling PA, Thomas L, Zhang FX, Kirschning CJ, et al. Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem. 2000;275:11058–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10753909.CrossRefGoogle Scholar
  102. 102.
    Zeuke S, Ulmer AJ, Kusumoto S, Katus HA, Heine H. TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS. Cardiovasc Res. 2002;56:126–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12237173.CrossRefGoogle Scholar
  103. 103.
    Verma S, Nakaoke R, Dohgu S, Banks WA. Release of cytokines by brain endothelial cells: a polarized response to lipopolysaccharide. Brain Behav Immun. 2006;20:449–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16309883.CrossRefGoogle Scholar
  104. 104.
    Fischer S, Nishio M, Peters SC, Tschernatsch M, Walberer M, Weidemann S, et al. Signaling mechanism of extracellular RNA in endothelial cells. FASEB J. 2009;23:2100–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19246491.CrossRefGoogle Scholar
  105. 105.
    El Kebir D, József L, Pan W, Wang L, Filep JG. Bacterial DNA activates endothelial cells and promotes neutrophil adherence through TLR9 signaling. J Immunol. 2009;182:4386–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19299739.CrossRefGoogle Scholar
  106. 106.
    Shin H-S, Xu F, Bagchi A, Herrup E, Prakash A, Valentine C, et al. Bacterial lipoprotein TLR2 agonists broadly modulate endothelial function and coagulation pathways in vitro and in vivo. J Immunol. 2011;186:1119–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21169547.CrossRefGoogle Scholar
  107. 107.
    Wilhelmsen K, Mesa KR, Prakash A, Xu F, Hellman J. Activation of endothelial TLR2 by bacterial lipoprotein upregulates proteins specific for the neutrophil response. Innate Immun. 2012;18:602–16. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22186927.CrossRefGoogle Scholar
  108. 108.
    Michels A, Albánez S, Mewburn J, Nesbitt K, Gould TJ, Liaw PC, et al. Histones link inflammation and thrombosis through the induction of Weibel-Palade Body exocytosis. J Thromb Haemost. 2016;14:2274. http://www.ncbi.nlm.nih.gov/pubmed/27589692 CrossRefGoogle Scholar
  109. 109.
    Alcock J, Brainard AH. Hemostatic containment - an evolutionary hypothesis of injury by innate immune cells. Med Hypotheses. 2008;71:960–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18718723.CrossRefGoogle Scholar
  110. 110.
    Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol. 2013;13:34–45. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23222502.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Yang X, Murthy V, Schultz K, Tatro JB, Fitzgerald KA, Beasley D. Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2006;291:H2334–43. Available from: http://ajpheart.physiology.org/cgi/doi/10.1152/ajpheart.00252.2006.CrossRefGoogle Scholar
  112. 112.
    Pi Y, Zhang L, Li B, Guo L, Cao X, Gao C, et al. Inhibition of reactive oxygen species generation attenuates TLR4-mediated proinflammatory and proliferative phenotype of vascular smooth muscle cells. Lab Invest. 2013;93:880–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23774581.CrossRefGoogle Scholar
  113. 113.
    Wen C, Yang X, Yan Z, Zhao M, Yue X, Cheng X, et al. Nalp3 inflammasome is activated and required for vascular smooth muscle cell calcification. Int J Cardiol. 2013;168:2242–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23453445.CrossRefGoogle Scholar
  114. 114.
    Imaizumi T, Yagihashi N, Hatakeyama M, Yamashita K, Ishikawa A, Taima K, et al. Expression of retinoic acid-inducible gene-I in vascular smooth muscle cells stimulated with interferon-gamma. Life Sci. 2004;75:1171–80. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0024320504003935.CrossRefGoogle Scholar
  115. 115.
    Hakimi M, Peters A, Becker A, Böckler D, Dihlmann S. Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis. J Vasc Surg. 2014;59:794–803. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0741521413007763.CrossRefGoogle Scholar
  116. 116.
    de Graaf R, Kloppenburg G, Kitslaar PJHM, Bruggeman CA, Stassen F. Human heat shock protein 60 stimulates vascular smooth muscle cell proliferation through Toll-like receptors 2 and 4. Microbes Infect. 2006;8:1859–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16843693.CrossRefGoogle Scholar
  117. 117.
    Porto A, Palumbo R, Pieroni M, Aprigliano G, Chiesa R, Sanvito F, et al. Smooth muscle cells in human atherosclerotic plaques secrete and proliferate in response to high mobility group box 1 protein. FASEB J. 2006;20:2565–6. Available from: http://www.fasebj.org/cgi/doi/10.1096/fj.06-5867fje.CrossRefGoogle Scholar
  118. 118.
    Chistiakov DA, Orekhov AN, Bobryshev YV. Vascular smooth muscle cell in atherosclerosis. Acta Physiol. 2015;214:33–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25677529.CrossRefGoogle Scholar
  119. 119.
    Cybulsky MI, Cheong C, Robbins CS. Macrophages and dendritic cells. Circ Res. 2016;118:637–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26892963.CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Johnson JL, Newby AC. Macrophage heterogeneity in atherosclerotic plaques. Curr Opin Lipidol. 2009;20:370–8. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00041433-200910000-00004.PubMedCentralCrossRefPubMedGoogle Scholar
  121. 121.
    Tabas I. 2016 Russell Ross memorial lecture in vascular biology. Arterioscler Thromb Vasc Biol. 2017;37:183. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27979856.CrossRefGoogle Scholar
  122. 122.
    Chinetti-Gbaguidi G, Colin S, Staels B. Macrophage subsets in atherosclerosis. Nat Rev Cardiol. 2014;12:10–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25367649.CrossRefGoogle Scholar
  123. 123.
    Decano JL, Mattson PC, Aikawa M. Macrophages in vascular inflammation: origins and functions. Curr Atheroscler Rep. 2016;18:34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27125207.CrossRefGoogle Scholar
  124. 124.
    Tabas I, Bornfeldt KE. Macrophage phenotype and function in different stages of atherosclerosis. Circ Res. 2016;118:653–67. Available from: http://circres.ahajournals.org/lookup/doi/10.1161/CIRCRESAHA.115.306256.PubMedCentralCrossRefPubMedGoogle Scholar
  125. 125.
    Shirai T, Hilhorst M, Harrison DG, Goronzy JJ, Weyand CM. Macrophages in vascular inflammation--from atherosclerosis to vasculitis. Autoimmunity. 2015;48:139–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25811915.PubMedCentralCrossRefPubMedGoogle Scholar
  126. 126.
    Kassiteridi C, Monaco C. Macrophages and dendritic cells: the usual suspects in atherogenesis. Curr Drug Targets. 2015;16:373–82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25808566.CrossRefGoogle Scholar
  127. 127.
    Swirski FK, Nahrendorf M, Libby P. Mechanisms of myeloid cell modulation of atherosclerosis. Microbiol Spectr. 2016;4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27726819.
  128. 128.
    Alberts-Grill N, Denning TL, Rezvan A, Jo H. The role of the vascular dendritic cell network in atherosclerosis. AJP Cell Physiol. 2013;305:C1–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23552284.CrossRefGoogle Scholar
  129. 129.
    Zernecke A. Dendritic cells in atherosclerosis significance. Arterioscler Thromb Vasc Biol. 2015;35:763–70. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25675999.CrossRefGoogle Scholar
  130. 130.
    van Osch GJVM, Brittberg M, Dennis JE, Bastiaansen-Jenniskens YM, Erben RG, Konttinen YT, et al. Cartilage repair: past and future--lessons for regenerative medicine. J Cell Mol Med. 2009;13:792–810. Available from: http://doi.wiley.com/10.1111/j.1582-4934.2009.00789.x.PubMedCentralCrossRefPubMedGoogle Scholar
  131. 131.
    Grogan SP, Miyaki S, Asahara H, D’Lima DD, Lotz MK. Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis. Arthritis Res Ther. 2009;11:R85. Available from: http://arthritis-research.biomedcentral.com/articles/10.1186/ar2719.PubMedCentralCrossRefPubMedGoogle Scholar
  132. 132.
    Sillat T, Barreto G, Clarijs P, Soininen A, Ainola M, Pajarinen J, et al. Toll-like receptors in human chondrocytes and osteoarthritic cartilage. Acta Orthop. 2013;84:585–92. Available from: http://www.tandfonline.com/doi/full/10.3109/17453674.2013.854666.PubMedCentralCrossRefPubMedGoogle Scholar
  133. 133.
    Jahr H, Matta C, Mobasheri A. Physicochemical and biomechanical stimuli in cell-based articular cartilage repair. Curr Rheumatol Rep. 2015;17:22. Available from: http://link.springer.com/10.1007/s11926-014-0493-9.PubMedCentralCrossRefPubMedGoogle Scholar
  134. 134.
    Muir H. The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules. Bioessays. 1995;17:1039–48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8634065.CrossRefGoogle Scholar
  135. 135.
    Del Carlo M, Loeser RF. Cell death in osteoarthritis. Curr Rheumatol Rep. 2008;10:37–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18457610.CrossRefGoogle Scholar
  136. 136.
    Komori T. Cell death in chondrocytes, osteoblasts, and osteocytes. Int J Mol Sci. 2016;17:2045. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27929439.PubMedCentralCrossRefPubMedGoogle Scholar
  137. 137.
    Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol. 2015;11:35–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25266449.CrossRefGoogle Scholar
  138. 138.
    Cecil DL, Johnson K, Rediske J, Lotz M, Schmidt AM, Terkeltaub R. Inflammation-induced chondrocyte hypertrophy is driven by receptor for advanced glycation end products. J Immunol. 2005;175:8296–302. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16339570.CrossRefGoogle Scholar
  139. 139.
    Yammani RR, Carlson CS, Bresnick AR, Loeser RF. Increase in production of matrix metalloproteinase 13 by human articular chondrocytes due to stimulation with S100A4: role of the receptor for advanced glycation end products. Arthritis Rheum. 2006;54:2901–11. Available from: http://doi.wiley.com/10.1002/art.22042.CrossRefGoogle Scholar
  140. 140.
    Nakahama K. Cellular communications in bone homeostasis and repair. Cell Mol Life Sci. 2010;67:4001–9. Available from: http://link.springer.com/10.1007/s00018-010-0479-3.CrossRefGoogle Scholar
  141. 141.
    Aubin JE. Regulation of osteoblast formation and function. Rev Endocr Metab Disord. 2001;2:81–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11704982.CrossRefGoogle Scholar
  142. 142.
    Lee S-H, Kim T-S, Choi Y, Lorenzo J. Osteoimmunology: cytokines and the skeletal system. BMB Rep. 2008;41:495–510. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18682033.PubMedCentralCrossRefPubMedGoogle Scholar
  143. 143.
    Li M-J, Li F, Xu J, Liu Y-D, Hu T, Chen J-T. rhHMGB1 drives osteoblast migration in a TLR2/TLR4- and NF- B-dependent manner. Biosci Rep. 2016;36:e00300. Available from: http://bioscirep.org/cgi/doi/10.1042/BSR20150239.PubMedCentralCrossRefPubMedGoogle Scholar
  144. 144.
    Li Q, Yu B, Yang P. Hypoxia-induced HMGB1 in would tissues promotes the osteoblast cell proliferation via activating ERK/JNK signaling. Int J Clin Exp Med. 2015;8:15087.PubMedCentralPubMedGoogle Scholar
  145. 145.
    Allaeys I, Marceau F, Poubelle PE. NLRP3 promotes autophagy of urate crystals phagocytized by human osteoblasts. Arthritis Res Ther. 2013;15:R176. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24456929.PubMedCentralCrossRefPubMedGoogle Scholar
  146. 146.
    Feng X, Teitelbaum SL. Osteoclasts: new insights. Bone Res. 2013;1:11–26. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26273491.CrossRefGoogle Scholar
  147. 147.
    Koh J-M, Lee Y-S, Kim YS, Park S-H, Lee SH, Kim H-H, et al. Heat shock protein 60 causes osteoclastic bone resorption via toll-like receptor-2 in estrogen deficiency. Bone. 2009;45:650–60. Available from: http://linkinghub.elsevier.com/retrieve/pii/S8756328209016366.CrossRefGoogle Scholar
  148. 148.
    Grevers LC, de Vries TJ, Vogl T, Abdollahi-Roodsaz S, Sloetjes AW, Leenen PJM, et al. S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll-like receptor 4: implications for bone destruction in murine antigen-induced arthritis. Arthritis Rheum. 2011;63:1365–75. Available from: http://doi.wiley.com/10.1002/art.30290.CrossRefGoogle Scholar
  149. 149.
    Kassem A, Henning P, Kindlund B, Lindholm C, Lerner UH. TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss. FASEB J. 2015;29:4449–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26207027.CrossRefGoogle Scholar
  150. 150.
    Kim S-J, Chen Z, Chamberlain ND, Essani AB, Volin MV, Amin MA, et al. Ligation of TLR5 promotes myeloid cell infiltration and differentiation into mature osteoclasts in rheumatoid arthritis and experimental arthritis. J Immunol. 2014;193:3902–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25200955.PubMedCentralCrossRefPubMedGoogle Scholar
  151. 151.
    Zhou Z, Xiong W-C. RAGE and its ligands in bone metabolism. Front Biosci (Schol Ed). 2011;3:768–76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21196410.Google Scholar
  152. 152.
    Zhou Z, Han J-Y, Xi C-X, Xie J-X, Feng X, Wang C-Y, et al. HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE. J Bone Miner Res. 2008;23:1084–96. Available from: http://doi.wiley.com/10.1359/jbmr.080234.PubMedCentralCrossRefPubMedGoogle Scholar
  153. 153.
    Schäffler A, Schölmerich J. Innate immunity and adipose tissue biology. Trends Immunol. 2010;31:228–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20434953.CrossRefGoogle Scholar
  154. 154.
    DiSpirito JR, Mathis D. Immunological contributions to adipose tissue homeostasis. Semin Immunol. 2015;27:315–21. Available from: http://linkinghub.elsevier.com/retrieve/pii/S104453231500069X.PubMedCentralCrossRefPubMedGoogle Scholar
  155. 155.
    Grant RW, Dixit VD. Adipose tissue as an immunological organ. Obesity. 2015;23:512–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25612251.CrossRefGoogle Scholar
  156. 156.
    Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9:367–77. Available from: http://www.nature.com/doifinder/10.1038/nrm2391.PubMedCentralCrossRefPubMedGoogle Scholar
  157. 157.
    Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19:1252–63. Available from: http://www.nature.com/doifinder/10.1038/nm.3361.CrossRefGoogle Scholar
  158. 158.
    Nedergaard J, Cannon B. The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab. 2010;11:268–72. Available from: http://linkinghub.elsevier.com/retrieve/pii/S155041311000077X.CrossRefGoogle Scholar
  159. 159.
    Schäffler A, Schölmerich J, Salzberger B. Adipose tissue as an immunological organ: toll-like receptors, C1q/TNFs and CTRPs. Trends Immunol. 2007;28:393–9. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1471490607001822.CrossRefGoogle Scholar
  160. 160.
    Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE. The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem. 2000;275:24255–63. Available from: http://www.jbc.org/cgi/doi/10.1074/jbc.M002137200.CrossRefGoogle Scholar
  161. 161.
    Vitseva OI, Tanriverdi K, Tchkonia TT, Kirkland JL, McDonnell ME, Apovian CM, et al. Inducible Toll-like receptor and NF-kappaB regulatory pathway expression in human adipose tissue. Obesity (Silver Spring). 2008;16:932–7. Available from: http://doi.wiley.com/10.1038/oby.2008.25.CrossRefGoogle Scholar
  162. 162.
    Jin C, Flavell RA. Innate sensors of pathogen and stress: linking inflammation to obesity. J Allergy Clin Immunol. 2013;132:287–94. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0091674913009901.CrossRefGoogle Scholar
  163. 163.
    Matzinger P. Friendly and dangerous signals: is the tissue in control? Nat Immunol. 2007;8(1):11–3. Available from: PubMed PMID: 17179963.CrossRefGoogle Scholar
  164. 164.
    Rivera A, Siracusa MC, Yap GS, Gause WC. Innate cell communication kick-starts pathogen-specific immunity. Nat Immunol. 2016;17:356–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27002843.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of StrasbourgMolecular ImmunoRheumatology, Laboratory of Excellence TransplantexStrasbourgFrance

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