Intestinal Permeability and Transport of Food Allergens

  • Linglin Fu
  • Bobby J. Cherayil
  • Haining Shi
  • Yanbo Wang
  • Yang Zhu


Serving as the predominant site for food digestion and nutrition absorption, the gastrointestinal tract separates the inner environment of the human body from the outer environment by epithelial barrier. The highly selective barrier favors fluxes of nutrients but limits host contact with the massive intraluminal load of dietary antigens and microbes. Under normal physiological conditions, controllable small amounts of food-derived antigens and microorganisms transport through the barrier with proper processing, inducting a homeostatic immune response and resulting in immune tolerance to dietary antigens. Conversely, primary or secondary intestinal barrier defects can lead to excessive entrance of lumen macromolecules, contributing to the pathogenesis of a wide range of human diseases including food allergy and inflammatory bowel disease (IBD). Consequently, the intestinal barrier dysfunction could be a promising target for treating food allergy; however, limited mechanical researches and practical applications are available nowadays, and far more investigations are required for reliable clinical practices.


  1. Adachi T, Stafford S, Kayaba H et al (2003) Myosin light chain kinase mediates eosinophil chemotaxis in a mitogen-activated protein kinase-dependent manner. J Allergy Clin Immunol 111:113–116. CrossRefPubMedGoogle Scholar
  2. Al-Ghouleh A, Johal R, Sharquie IK et al (2012) The glycosylation pattern of common allergens: the recognition and uptake of Der p 1 by epithelial and dendritic cells is carbohydrate dependent. PLoS One 7:e33929. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Al-Sadi R, Khatib K, Guo S et al (2011) Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier. Am J Physiol Gastrointest Liver Physiol 300:G1054–G1064. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Al-Sadi R, Rawat M, Ma TY (2017) Mmp-9 modulation of intestinal epithelial tight junction barrier in-vitro and in-vivo is mediated by myosin light chain kinase (mlck). Gastroenterology 152:S559–S559. CrossRefGoogle Scholar
  5. Al-Sadi R, Rawat M, Ma T (2018) Mechanism of Mmp-9 activation of myosin light chain kinase (mlck) mediated disruption of intestinal tight junction barrier. Inflamm Bowel Dis 24:S26–S26. CrossRefGoogle Scholar
  6. Amasheh M, Grotjohann I, Amasheh S et al (2009) Regulation of mucosal structure and barrier function in rat colon exposed to tumor necrosis factor alpha and interferon gamma in vitro: a novel model for studying the pathomechanisms of inflammatory bowel disease cytokines. Scand J Gastroenterol 44:1226–1235. CrossRefPubMedGoogle Scholar
  7. Astwood JD, Leach JN, Fuchs RL (1996) Stability of food allergens to digestion in vitro. Nat Biotechnol 14:1269–1273. CrossRefPubMedGoogle Scholar
  8. Balda MS, Whitney JA, Flores C et al (1996) Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J Cell Biol 134:1031. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Balda MS, Flores-Maldonado C, Cereijido M, Matter K (2000) Multiple domains of occludin are involved in the regulation of paracellular permeability. J Cell Biochem 78:85–96.<85::AID-JCB8>3.0.CO;2-F CrossRefPubMedGoogle Scholar
  10. Bannert C, Bidmon-Fliegenschnee B, Stary G et al (2012) Fc-epsilon-RI, the high affinity IgE-receptor, is robustly expressed in the upper gastrointestinal tract and modulated by mucosal inflammation. PLoS One 7:e42066. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Barbaro MR, Dino P, Carapelle M et al (2016) Escherichia coli Nissle 1917 reinforces intestinal epithelial barrier and prevents permeability alterations induced by cytokines and PAR-2 activation: an in vitro study. Gastroenterology 150:S498–S498. CrossRefGoogle Scholar
  12. Barrett NA, Rahman OM, Fernandez JM et al (2011) Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes. J Exp Med 208:593–604. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Berin MC (2012) Mucosal antibodies in the regulation of tolerance and allergy to foods. Semin Immunopathol 34:633–642. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Berin MC, Yang PC, Ciok L et al (1999) Role for IL-4 in macromolecular transport across human intestinal epithelium. Am J Phys 276:C1046–C1052CrossRefGoogle Scholar
  15. Berin MC, Zheng Y, Domaradzki M et al (2006) Role of TLR4 in allergic sensitization to food proteins in mice. Allergy 61:64–71. CrossRefPubMedGoogle Scholar
  16. Botos I, Segal DM, Davies DR (2011) The structural biology of toll-like receptors. Structure 19:447–459. CrossRefPubMedPubMedCentralGoogle Scholar
  17. Buschmann MM, Shen L, Rajapakse H et al (2013) Occludin OCEL-domain interactions are required for maintenance and regulation of the tight junction barrier to macromolecular flux. Mol Biol Cell 24:3056–3068. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Capaldo CT, Powell DN, Kalman D (2017) Layered defense: how mucus and tight junctions seal the intestinal barrier. J Mol Med 95:927–934. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Cenac N, Chin AC, Garcia-Villar R et al (2004) PAR2 activation alters colonic paracellular permeability in mice via IFN-gamma-dependent and -independent pathways. J Physiol 558:913–925. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Ceponis PJ, Botelho F, Richards CD, McKay DM (2000) Interleukins 4 and 13 increase intestinal epithelial permeability by a phosphatidylinositol 3-kinase pathway. Lack of evidence for STAT 6 involvement. J Biol Chem 275:29132–29137. CrossRefPubMedGoogle Scholar
  21. Chen H-Y, Sharma BB, Yu L et al (2006) Role of galectin-3 in mast cell functions: galectin-3-deficient mast cells exhibit impaired mediator release and defective JNK expression. J Immunol (Baltim Md 1950) 177:4991–4997CrossRefGoogle Scholar
  22. Chen C, Wang P, Su Q et al (2012) Myosin light chain kinase mediates intestinal barrier disruption following burn injury. PLoS One 7:e34946. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Chieppa M, Rescigno M, Huang AYC, Germain RN (2006) Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J Exp Med 203:2841–2852. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Chiou Y-L, Lin C-Y (2009) Der p2 activates airway smooth muscle cells in a TLR2/MyD88-dependent manner to induce an inflammatory response. J Cell Physiol 220:311–318. CrossRefPubMedGoogle Scholar
  25. Clayburgh DR, Barrett TA, Tang Y et al (2005) Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J Clin Invest 115:2702–2715. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Clayburgh DR, Musch MW, Leitges M et al (2006) Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo. J Clin Investig 116:2682–2694. CrossRefPubMedGoogle Scholar
  27. Corey R (2010) Nutritional protocol for the treatment of intestinal permeability defects and related conditions. Natl Med J 2:14–23Google Scholar
  28. Cubells-Baeza N, Verhoeckx KCM, Larre C et al (2015) Applicability of epithelial models in protein permeability/transport studies and food allergy. Drug Discov Today Dis Models 17–18:13–21. CrossRefGoogle Scholar
  29. Cunningham KE, Turner JR (2012) Myosin light chain kinase: pulling the strings of epithelial tight junction function. In: Fromm M, Schulzke JD (eds) Barriers and channels formed by tight junction proteins ii. Blackwell Science Publishing, Oxford, pp 34–42Google Scholar
  30. Day SB, Ledford JR, Zhou P et al (2012) German cockroach proteases and protease-activated receptor-2 regulate chemokine production and dendritic cell recruitment. J Innate Immun 4:100–110. CrossRefPubMedGoogle Scholar
  31. Di Leo V, Yang P-C, Berin MC, Perdue MH (2002) Factors regulating the effect of IL-4 on intestinal epithelial barrier function. Int Arch Allergy Immunol 129:219–227. CrossRefPubMedGoogle Scholar
  32. Diamond JM (1974) Tight and leaky junctions of epithelia: a perspective on kisses in the dark. Fed Proc 33:2220–2224PubMedGoogle Scholar
  33. Dickinson BL, Badizadegan K, Wu Z et al (1999) Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J Clin Invest 104(7):903–911CrossRefGoogle Scholar
  34. Eisenbarth SC, Piggott DA, Huleatt JW et al (2002) Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med 196:1645–1651CrossRefGoogle Scholar
  35. Forbes EE, Groschwitz K, Abonia JP et al (2008) IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med 205:897–913. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Fordham RP, Yui S, Hannan NRF et al (2013) Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury. Cell Stem Cell 13:734–744. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Freier S, Lebenthal E, Freier M et al (1983) IgE and IgD antibodies to cow milk and soy protein in duodenal fluid: effects of pancreozymin and secretin. Immunology 49:69–75PubMedPubMedCentralGoogle Scholar
  38. Fu L, Wang C, Wang Y (2018) Seafood allergen-induced hypersensitivity at the microbiota-mucosal site: implications for prospective probiotic use in allergic response regulation. Crit Rev Food Sci Nutr 58(9):1512–1525. CrossRefPubMedGoogle Scholar
  39. Furuse M, Hirase T, Itoh M et al (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123:1777. CrossRefPubMedGoogle Scholar
  40. González-Mariscal L, Garay E, Quiros M (2010) Regulation of Claudins by posttranslational modifications and cell-signaling cascades. Curr Top Membr 65:113–150. CrossRefGoogle Scholar
  41. Gustafsson J, Wising C, Ermund A et al (2017) Goblet cell mediated antigen delivery to the immune system is linked to mucus secretion and dependent on a functional Cftr channel. Gastroenterology 152:S24–S24. CrossRefGoogle Scholar
  42. Hattori T, Konno S, Hizawa N et al (2009) Genetic variants in the mannose receptor gene (MRC1) are associated with asthma in two independent populations. Immunogenetics 61:731–738. CrossRefPubMedGoogle Scholar
  43. He W, Peng Y, Zhang W et al (2008) Myosin light chain kinase is central to smooth muscle contraction and required for gastrointestinal motility in mice. Gastroenterology 135:610–620.e2. CrossRefPubMedPubMedCentralGoogle Scholar
  44. He W-Q, Qiao Y-N, Zhang C-H et al (2011) Role of myosin light chain kinase in regulation of basal blood pressure and maintenance of salt-induced hypertension. Am J Physiol Heart Circ Physiol 301:H584–H591. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Heller F, Florian P, Bojarski C et al (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129:550–564. CrossRefPubMedGoogle Scholar
  46. Heller F, Fromm A, Gitter AH et al (2008) Epithelial apoptosis is a prominent feature of the epithelial barrier disturbance in intestinal inflammation: effect of pro-inflammatory interleukin-13 on epithelial cell function. Mucosal Immunol 1(Suppl 1):S58–S61. CrossRefPubMedGoogle Scholar
  47. Henningsson F, Ding Z, Dahlin JS et al (2011) IgE-mediated enhancement of CD4+ T cell responses in mice requires antigen presentation by CD11c+ cells and not by B cells. PLoS One 6:e21760. CrossRefPubMedPubMedCentralGoogle Scholar
  48. Herre J, Gronlund H, Brooks H et al (2013) Allergens as immunomodulatory proteins: the cat dander protein Fel d 1 enhances TLR activation by lipid ligands. J Immunol 191:1529–1535. CrossRefPubMedGoogle Scholar
  49. Heyman M (2005) Gut barrier dysfunction in food allergy. Eur J Gastroenterol Hepatol 17:1279–1285CrossRefGoogle Scholar
  50. Heyman M, Ménard S (2009) Pathways of gliadin transport in celiac disease. Ann N Y Acad Sci 1165:274–278. CrossRefPubMedGoogle Scholar
  51. Heyman M, Ducroc R, Desjeux JF, Morgat JL (1982) Horseradish peroxidase transport across adult rabbit jejunum in vitro. Am J Phys 242:G558–G564. CrossRefGoogle Scholar
  52. Heyman M, Bonfils A, Fortier M et al (1987) Intestinal absorption of RU 41740, an immunomodulating compound extracted from Klebsiella pneumoniae, across duodenal epithelium and Peyer’s patches of the rabbit. Int J Pharm 37:33–39. CrossRefGoogle Scholar
  53. Heyman M, Grasset E, Ducroc R, Desjeux J-F (1988) Antigen absorption by the jejunal epithelium of children with cow’s milk allergy. Pediatr Res 24:197–202. CrossRefPubMedGoogle Scholar
  54. Himly M, Jahn-Schmid B, Dedic A et al (2003) Art v 1, the major allergen of mugwort pollen, is a modular glycoprotein with a defensin-like and a hydroxyproline-rich domain. FASEB J 17:106–108. CrossRefPubMedGoogle Scholar
  55. Hollenberg MD, Mihara K, Polley D et al (2014) Biased signalling and proteinase-activated receptors (PARs): targeting inflammatory disease. Br J Pharmacol 171:1180–1194. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Houska M, Setinova I, Kucera P (2013) Food allergens and processing: a review of recent results. In: Yanniotis S, Taoukis P, Stoforos NG, Karathanos VT (eds) Advances in food process engineering research and applications. Springer US, Boston, pp 291–337CrossRefGoogle Scholar
  57. Iacovacci P, Afferni C, Butteroni C et al (2002) Comparison between the native glycosylated and the recombinant Cup a1 allergen: role of carbohydrates in the histamine release from basophils. Clin Exp Allergy 32:1620–1627CrossRefGoogle Scholar
  58. Ikenouchi J, Furuse M, Furuse K et al (2005) Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 171:939. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Ikenouchi J, Sasaki H, Tsukita S et al (2008) Loss of occludin affects tricellular localization of tricellulin. Mol Biol Cell 19:4687–4693. CrossRefPubMedPubMedCentralGoogle Scholar
  60. Ino S, Kohda C, Takeshima K et al (2016) Oral tolerance is inducible during active dextran sulfate sodium-induced colitis. World J Gastrointest Pharmacol Ther 7:242–253. CrossRefPubMedPubMedCentralGoogle Scholar
  61. Jacob C, Yang P-C, Darmoul D et al (2005) Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins. J Biol Chem 280:31936–31948. CrossRefPubMedGoogle Scholar
  62. Jalonen T (1991) Identical intestinal permeability changes in children with different clinical manifestations of cow’s milk allergy. J Allergy Clin Immunol 88:737–742. CrossRefPubMedGoogle Scholar
  63. Johansson MEV, Larsson JMH, Hansson GC (2011) The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci 108:4659–4665. CrossRefPubMedGoogle Scholar
  64. Jones EA, Waldmann TA (1972) The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. J Clin Invest 51:2916–2927. CrossRefPubMedPubMedCentralGoogle Scholar
  65. Judaki A, Hafeziahmadi M, Yousefi A et al (2014) Evaluation of dairy allergy among ulcerative colitis patients. Bioinformation 10:693–696. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Kaiserlian D, Lachaux A, Grosjean I et al (1993) Intestinal epithelial cells express the CD23/FcεRII molecule: enhanced expression in enteropathies. Immunology 80:90–95PubMedPubMedCentralGoogle Scholar
  67. Katoh S, Ishii N, Nobumoto A et al (2007) Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of allergic asthma. Am J Respir Crit Care Med 176:27–35. CrossRefPubMedGoogle Scholar
  68. Kawaguchi T, Mori M, Saito K et al (2015) Food antigen-induced immune responses in Crohn’s disease patients and experimental colitis mice. J Gastroenterol 50:394–405. CrossRefPubMedGoogle Scholar
  69. Kehry MR, Yamashita LC (1989) Low-affinity IgE receptor (CD23) function on mouse B cells: role in IgE-dependent antigen focusing. Proc Natl Acad Sci U S A 86:7556–7560CrossRefGoogle Scholar
  70. Keita ÅV, Gullberg E, Ericson A-C et al (2006) Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum. Lab Investig 86:504–516. CrossRefPubMedGoogle Scholar
  71. Kim YS, Ho SB (2010) Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep 12:319–330. CrossRefPubMedPubMedCentralGoogle Scholar
  72. Kimura S (2018) Molecular insights into the mechanisms of M-cell differentiation and transcytosis in the mucosa-associated lymphoid tissues. Anat Sci Int 93:23–34. CrossRefPubMedGoogle Scholar
  73. Kitajiri S-I, Katsuno T, Sasaki H et al (2014) Deafness in occludin-deficient mice with dislocation of tricellulin and progressive apoptosis of the hair cells. Biol Open 3:759–766. CrossRefPubMedPubMedCentralGoogle Scholar
  74. Kitani S, Teshima R, Morita Y et al (1992) Inhibition of IgE-mediated histamine release by myosin light chain kinase inhibitors. Biochem Biophys Res Commun 183:48–54. CrossRefPubMedGoogle Scholar
  75. Knoop KA, Miller MJ, Newberry RD (2013) Transepithelial antigen delivery in the small intestine: different paths, different outcomes. Curr Opin Gastroenterol 29:112–118. CrossRefPubMedPubMedCentralGoogle Scholar
  76. Konig J, Wells J, Cani PD et al (2016) Human intestinal barrier function in health and disease. Clin Transl Gastroenterol 7:e196. CrossRefPubMedPubMedCentralGoogle Scholar
  77. Krug SM, Amasheh S, Richter JF et al (2009) Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability. Mol Biol Cell 20:3713–3724. CrossRefPubMedPubMedCentralGoogle Scholar
  78. Krug SM, Schulzke JD, Fromm M (2014) Tight junction, selective permeability, and related diseases. Semin Cell Dev Biol 36:166–176. CrossRefPubMedGoogle Scholar
  79. Li H, Nowak-Wegrzyn A, Charlop-Powers Z et al (2006) Transcytosis of IgE-antigen complexes by CD23a in human intestinal epithelial cells and its role in food allergy. Gastroenterology 131:47–58. CrossRefPubMedGoogle Scholar
  80. Li H, Chehade M, Liu W et al (2007) Allergen-IgE complexes trigger CD23-dependent CCL20 release from human intestinal epithelial cells. Gastroenterology 133:1905–1915. CrossRefPubMedPubMedCentralGoogle Scholar
  81. Li L-J, Zeng L, Li X-X et al (2016) Induction of colitis in mice with food allergen-specific immune response. Sci Rep 6:32765. CrossRefPubMedPubMedCentralGoogle Scholar
  82. Lianto P, Han S, Li X et al (2018) Quail egg homogenate alleviates food allergy induced eosinophilic esophagitis like disease through modulating PAR-2 transduction pathway in peanut sensitized mice. Sci Rep 8:1049. CrossRefPubMedPubMedCentralGoogle Scholar
  83. Liu C-K, Chen C-A, Lee T-Y et al (2018) Rice protein prolamin promotes anti-leukemia immunity and inhibits leukemia growth in vivo. Food Chem Toxicol 112:435–440. CrossRefPubMedGoogle Scholar
  84. Mahraoui L, Heyman M, Plique O et al (1997) Apical effect of diosmectite on damage to the intestinal barrier induced by basal tumour necrosis factor-alpha. Gut 40:339–343CrossRefGoogle Scholar
  85. Marchiando AM, Shen L, Graham WV et al (2010) Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo. J Cell Biol 189:111–126. CrossRefPubMedPubMedCentralGoogle Scholar
  86. Matysiak-Budnik T, Moura IC, Arcos-Fajardo M et al (2008) Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J Exp Med 205:143–154. CrossRefPubMedPubMedCentralGoogle Scholar
  87. McDole JR, Wheeler LW, McDonald KG et al (2012) Goblet cells deliver luminal antigen to CD103(+) dendritic cells in the small intestine. Nature 483:345–U141. CrossRefPubMedPubMedCentralGoogle Scholar
  88. Ménard S, Cerf-Bensussan N, Heyman M (2010) Multiple facets of intestinal permeability and epithelial handling of dietary antigens. Mucosal Immunol 3:247–259. CrossRefPubMedGoogle Scholar
  89. Mercer N, Guzman L, Cueto Rua E et al (2009) Duodenal intraepithelial lymphocytes of children with cow milk allergy preferentially bind the glycan-binding protein galectin-3. Int J Immunopathol Pharmacol 22:207–217. CrossRefPubMedPubMedCentralGoogle Scholar
  90. Nathan AT, Peterson EA, Chakir J, Wills-Karp M (2009) Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways. J Allergy Clin Immunol 123:612–618. CrossRefPubMedPubMedCentralGoogle Scholar
  91. Nayak G, Lee SI, Yousaf R et al (2013) Tricellulin deficiency affects tight junction architecture and cochlear hair cells. J Clin Invest 123:4036–4049. CrossRefPubMedPubMedCentralGoogle Scholar
  92. Niess JH, Brand S, Gu X et al (2005) CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254–258. CrossRefPubMedGoogle Scholar
  93. Nighot MP, Mccarthy DM, Ma TY (2017) Proton Pump Inhibitors (ppi) induces increase in gastric epithelial tight junction permeability via activation of myosin light-chain kinase. Gastroenterology 152:S888–S888. CrossRefGoogle Scholar
  94. Niki T, Tsutsui S, Hirose S et al (2009) Galectin-9 is a high affinity IgE-binding lectin with anti-allergic effect by blocking IgE-antigen complex formation. J Biol Chem 284:32344–32352. CrossRefPubMedPubMedCentralGoogle Scholar
  95. Odenwald MA, Turner JR (2017) The intestinal epithelial barrier: a therapeutic target? Nat Rev Gastroenterol Hepatol 14:9–21. CrossRefPubMedGoogle Scholar
  96. Pali-Schoell I, Jensen-Jarolim E (2011) Anti-acid medication as a risk factor for food allergy. Allergy 66:469–477. CrossRefGoogle Scholar
  97. Pirron U, Schlunck T, Prinz JC, Rieber EP (1990) IgE-dependent antigen focusing by human B lymphocytes is mediated by the low-affinity receptor for IgE. Eur J Immunol 20:1547–1551. CrossRefPubMedGoogle Scholar
  98. Pizzuti D, Senzolo M, Buda A et al (2011) In vitro model for IgE mediated food allergy. Scand J Gastroenterol 46:177–187. CrossRefPubMedGoogle Scholar
  99. Raleigh DR, Marchiando AM, Zhang Y et al (2010) Tight junction-associated MARVEL proteins marvelD3, tricellulin, and occludin have distinct but overlapping functions. Mol Biol Cell 21:1200–1213. CrossRefPubMedPubMedCentralGoogle Scholar
  100. Raleigh DR, Boe DM, Yu D et al (2011) Occludin S408 phosphorylation regulates tight junction protein interactions and barrier function. J Cell Biol 193:565–582. CrossRefPubMedPubMedCentralGoogle Scholar
  101. Rescigno M, Urbano M, Valzasina B et al (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361–367. CrossRefPubMedGoogle Scholar
  102. Roxas JL, Koutsouris A, Bellmeyer A et al (2010) Enterohemorrhagic E. coli alters murine intestinal epithelial tight junction protein expression and barrier function in a Shiga toxin independent manner. Lab Invest 90:1152–1168. CrossRefPubMedPubMedCentralGoogle Scholar
  103. Ruethers T, Raith M, Sharp MF et al (2018) Characterization of Rask1 a novel major allergen in Indian mackerel and identification of parvalbumin as the major fish allergen in 33 Asia-Pacific fish species. Clin Exp Allergy 48:452–463. CrossRefPubMedGoogle Scholar
  104. Saegusa J, Hsu DK, Chen H-Y et al (2009) Galectin-3 is critical for the development of the allergic inflammatory response in a mouse model of atopic dermatitis. Am J Pathol 174:922–931. CrossRefPubMedPubMedCentralGoogle Scholar
  105. Sakakibara A, Furuse M, Saitou M et al (1997) Possible involvement of phosphorylation of occludin in tight junction formation. J Cell Biol 137:1393CrossRefGoogle Scholar
  106. Salazar F, Ghaemmaghami A (2013) Allergen recognition by innate immune cells: critical role of dendritic and epithelial cells. Front Immunol 4:356. CrossRefPubMedPubMedCentralGoogle Scholar
  107. Salazar F, Sewell HF, Shakib F, Ghaemmaghami AM (2013) The role of lectins in allergic sensitization and allergic disease. J Allergy Clin Immunol 132:27–36. CrossRefPubMedGoogle Scholar
  108. Salazar F, Dawkins-Hall L, Negm O et al (2015) The mannose receptor negatively modulates the toll-like receptor 4-aryl hydrocarbon receptor-indoleamine 2,3-dioxygenase axis in dendritic cells affecting T helper cell polarization. J Allergy Clin Immunol 137:1841–1851.e2. CrossRefPubMedGoogle Scholar
  109. Sancho D, Reis e Sousa C (2012) Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol 30:491–529. CrossRefPubMedPubMedCentralGoogle Scholar
  110. Sato T, Vries RG, Snippert HJ et al (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–265. CrossRefPubMedGoogle Scholar
  111. Scala E, Villalta D, Meneguzzi G et al (2018) Storage molecules from tree nuts, seeds and legumes: relationships and amino acid identity among homologue molecules. Eur Ann Allergy Clin Immunol 50(4):148–155. CrossRefPubMedGoogle Scholar
  112. Shen L, Black ED, Witkowski ED et al (2006) Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. J Cell Sci 119:2095. CrossRefPubMedPubMedCentralGoogle Scholar
  113. Sheth B, Moran B, Anderson JM, Fleming TP (2000) Post-translational control of occludin membrane assembly in mouse trophectoderm: a mechanism to regulate timing of tight junction biogenesis and blastocyst formation. Development 127:831–840PubMedGoogle Scholar
  114. Shigetomi K, Ikenouchi J (2018) Regulation of the epithelial barrier by post-translational modifications of tight junction membrane proteins. J Biochem (Tokyo) 163:265–272. CrossRefGoogle Scholar
  115. Singh H, Gallier S (2014) Chapter 2 – Processing of food structures in the gastrointestinal tract and physiological responses. In: Food structures, digestion and health. Academic, San Diego, pp 51–81CrossRefGoogle Scholar
  116. Singh K, Chang C, Gershwin ME (2014) IgA deficiency and autoimmunity. Autoimmun Rev 13:163–177. CrossRefPubMedGoogle Scholar
  117. Steed E, Elbediwy A, Vacca B et al (2014) MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival. J Cell Biol 204:821–838. CrossRefPubMedPubMedCentralGoogle Scholar
  118. Stelekati E, Bahri R, D’Orlando O et al (2009) Mast cell-mediated antigen presentation regulates CD8+ T cell effector functions. Immunity 31:665–676. CrossRefPubMedGoogle Scholar
  119. Strauman MC, Harper JM, Harrington SM et al (2010) Enteroaggregative Escherichia coli disrupts epithelial cell tight junctions. Infect Immun 78:4958–4964. CrossRefPubMedPubMedCentralGoogle Scholar
  120. Su L, Nalle SC, Shen L et al (2013) TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology 145:407–415. CrossRefPubMedPubMedCentralGoogle Scholar
  121. Sung S-SJ, Fu SM, Rose CE et al (2006) A major lung CD103 (αE)-β7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. J Immunol 176:2161–2172. CrossRefPubMedGoogle Scholar
  122. Susanne J, Sonnhild M, Juliane R et al (2017) Tricellulin is a target of the ubiquitin ligase Itch. Ann N Y Acad Sci 1397:157–168. CrossRefGoogle Scholar
  123. Sziksz E, Kozma GT, Pállinger E et al (2010) Galectin-9 in allergic airway inflammation and hyper-responsiveness in mice. Int Arch Allergy Immunol 151:308–317. CrossRefPubMedGoogle Scholar
  124. Tanabe S (2012) Short peptide modules for enhancing intestinal barrier function. Curr Pharm Des 18:776–781. CrossRefPubMedGoogle Scholar
  125. Traweger A, Fang D, Liu Y-C et al (2002) The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch. J Biol Chem 277:10201–10208. CrossRefPubMedGoogle Scholar
  126. Troeger H, Loddenkemper C, Schneider T et al (2009) Structural and functional changes of the duodenum in human norovirus infection. Gut 58(8):1070–1077. CrossRefPubMedGoogle Scholar
  127. Trompette A, Divanovic S, Visintin A et al (2009) Allergenicity resulting from functional mimicry of a toll-like receptor complex protein. Nature 457:585–588. CrossRefPubMedGoogle Scholar
  128. Tu Y, Salim S, Bourgeois J et al (2005) CD23-mediated IgE transport across human intestinal epithelium: inhibition by blocking sites of translation or binding. Gastroenterology 129:928–940. CrossRefPubMedGoogle Scholar
  129. Turner JR, Buschmann MM, Romero-Calvo I et al (2014) The role of molecular remodeling in differential regulation of tight junction permeability. Semin Cell Dev Biol 36:204–212. CrossRefPubMedGoogle Scholar
  130. Untersmayr E, Jensen-Jarolim E (2008) The role of protein digestibility and antacids on food allergy outcomes. J Allergy Clin Immunol 121:1301–1308. CrossRefPubMedPubMedCentralGoogle Scholar
  131. Untersmayr E, Scholl I, Swoboda I et al (2003) Antacid medication inhibits digestion of dietary proteins and causes food allergy: a fish allergy model in BALB/c mice. J Allergy Clin Immunol 112:616–623. CrossRefPubMedGoogle Scholar
  132. Vacca B, Sanchez-Heras E, Steed E et al (2018) Control of neural crest induction by MarvelD3-mediated attenuation of JNK signalling. Sci Rep 8:1204. CrossRefPubMedPubMedCentralGoogle Scholar
  133. Van Spaendonk H, Ceuleers H, Witters L et al (2017) Regulation of intestinal permeability: the role of proteases. World J Gastroenterol 23:2106–2123. CrossRefPubMedPubMedCentralGoogle Scholar
  134. Vancamelbeke M, Vermeire S (2017) The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol 11:821–834. CrossRefPubMedPubMedCentralGoogle Scholar
  135. Virta LJ, Ashorn M, Kolho K-L (2013) Cow’s milk allergy, asthma, and pediatric IBD. J Pediatr Gastroenterol Nutr 56:649–651. CrossRefPubMedGoogle Scholar
  136. Wheeler EE, Challacombe DN, Kerry PJ, Pearson EC (1993) A morphological study of β-lactoglobulin absorption by cultured explants of the human duodenal mucosa using immunocytochemical and cytochemical techniques. J Pediatr Gastroenterol Nutr 16:157–164. CrossRefPubMedGoogle Scholar
  137. Wijngaard RMVD, Klooker TK, Welting O et al (2009) Essential role for TRPV1 in stress-induced (mast cell-dependent) colonic hypersensitivity in maternally separated rats. Neurogastroenterol Motil 21:1107–1e94. CrossRefPubMedGoogle Scholar
  138. Yamaoka T, Yan F, Cao H et al (2008) Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis. Proc Natl Acad Sci 105:11772. CrossRefPubMedGoogle Scholar
  139. Yang P-C, Jury J, Söderholm JD et al (2006) Chronic psychological stress in rats induces intestinal sensitization to luminal antigens. Am J Pathol 168:104–114. CrossRefPubMedPubMedCentralGoogle Scholar
  140. Yu D, Turner JR (2008) Stimulus-induced reorganization of tight junction structure: the role of membrane traffic. Biochim Biophys Acta 1778:709–716. CrossRefPubMedGoogle Scholar
  141. Yui S, Nakamura T, Sato T et al (2012) Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell. Nat Med 18:618–623. CrossRefPubMedGoogle Scholar
  142. Zeissig S, Bürgel N, Günzel D et al (2007) Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut 56:61–72. CrossRefPubMedPubMedCentralGoogle Scholar
  143. Zhang W-C, Peng Y-J, Zhang G-S et al (2010) Myosin light chain kinase is necessary for tonic airway smooth muscle contraction. J Biol Chem 285:5522–5531. CrossRefPubMedGoogle Scholar
  144. Zhao J, de Vera J, Narushima S et al (2007) R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice. Gastroenterology 132:1331–1343. CrossRefPubMedGoogle Scholar
  145. Zolotarevsky Y, Hecht G, Koutsouris A et al (2002) A membrane-permeant peptide that inhibits MLC kinase restores barrier function in in vitro models of intestinal disease. Gastroenterology 123:163–172. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Linglin Fu
    • 1
  • Bobby J. Cherayil
    • 2
  • Haining Shi
    • 2
  • Yanbo Wang
    • 1
  • Yang Zhu
    • 3
  1. 1.School of Food Science and BiotechnologyZhejiang Gongshang UniversityHanghzouChina
  2. 2.Mucosal Immunology and Biology ResearchHarvard Medical SchoolCharlestownUSA
  3. 3.Bioprocess Engineering Group, Agrotechnology and Food SciencesWageningen University and ResearchWageningenThe Netherlands

Personalised recommendations