1932

Abstract

The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well as other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. The intestinal mucosa is covered by mucin, which contains antimicrobial peptides and secretory IgA and prevents luminal bacteria, fungi, and viruses from stimulating intestinal immune responses. Conversely, the transport of luminal microorganisms—mediated by M, dendritic, and goblet cells—into intestinal tissues facilitates the harmonization of active and quiescent mucosal immune responses. The bacterial population within gut-associated lymphoid tissues creates the intratissue cohabitations for harmonized mucosal immunity. Intermolecular and intercellular communication among epithelial, immune, and mesenchymal cells creates an environment conducive for epithelial regeneration and mucosal healing. This review summarizes the so-called intestinal mucosal ecological network—the complex but vital molecular and cellular interactions of epithelial mesenchymal cells, immune cells, and commensal microbiota that achieve intestinal homeostasis, regeneration, and healing.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-051116-052424
2017-04-26
2024-10-14
Loading full text...

Full text loading...

/deliver/fulltext/immunol/35/1/annurev-immunol-051116-052424.html?itemId=/content/journals/10.1146/annurev-immunol-051116-052424&mimeType=html&fmt=ahah

Literature Cited

  1. Caballero S, Pamer EG. 1.  2015. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annu. Rev. Immunol. 33:227–56 [Google Scholar]
  2. Berg RD. 2.  1996. The indigenous gastrointestinal microflora. Trends Microbiol 4:430–35 [Google Scholar]
  3. Pfeiffer JK, Virgin HW. 3.  2016. Viral immunity: transkingdom control of viral infection and immunity in the mammalian intestine. Science 351:6270 doi: 10.1126/science.aad5872 [Google Scholar]
  4. Duerkop BA, Hooper LV. 4.  2013. Resident viruses and their interactions with the immune system. Nat. Immunol. 14:654–59 [Google Scholar]
  5. Huffnagle GB, Noverr MC. 5.  2013. The emerging world of the fungal microbiome. Trends Microbiol 21:334–41 [Google Scholar]
  6. Underhill DM, Pearlman E. 6.  2015. Immune interactions with pathogenic and commensal fungi: a two-way street. Immunity 43:845–58 [Google Scholar]
  7. Honda K, Littman DR. 7.  2012. The microbiome in infectious disease and inflammation. Annu. Rev. Immunol. 30:759–95 [Google Scholar]
  8. Mani S, Boelsterli UA, Redinbo MR. 8.  2014. Understanding and modulating mammalian-microbial communication for improved human health. Annu. Rev. Pharmacol. Toxicol. 54:559–80 [Google Scholar]
  9. Peterson LW, Artis D. 9.  2014. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14:141–53 [Google Scholar]
  10. Goto Y, Kiyono H. 10.  2012. Epithelial barrier: an interface for the cross-communication between gut flora and immune system. Immunol. Rev. 245:147–63 [Google Scholar]
  11. Karam SM. 11.  1999. Lineage commitment and maturation of epithelial cells in the gut. Front. Biosci. 4:D286–98 [Google Scholar]
  12. Jensen J, Pedersen EE, Galante P, Hald J, Heller RS. 12.  et al. 2000. Control of endodermal endocrine development by Hes-1. Nat. Genet. 24:36–44 [Google Scholar]
  13. Koo BK, Clevers H. 13.  2014. Stem cells marked by the R-spondin receptor LGR5. Gastroenterology 147:289–302 [Google Scholar]
  14. Bostick JW, Zhou L. 14.  2016. Innate lymphoid cells in intestinal immunity and inflammation. Cell Mol. Life Sci. 73:237–52 [Google Scholar]
  15. Bulek K, Swaidani S, Aronica M, Li X. 15.  2010. Epithelium: the interplay between innate and Th2 immunity. Immunol. Cell Biol. 88:257–68 [Google Scholar]
  16. Brenchley JM, Douek DC. 16.  2012. Microbial translocation across the GI tract. Annu. Rev. Immunol. 30:149–73 [Google Scholar]
  17. Schulz O, Pabst O. 17.  2013. Antigen sampling in the small intestine. Trends Immunol 34:155–61 [Google Scholar]
  18. Kiyono H, McGhee JR, Wannemuehler MJ, Frangakis MV, Spalding DM. 18.  et al. 1982. In vivo immune response to a T-cell-dependent antigen by cultures of disassociated murine Peyer's patch. PNAS 79:596–600 [Google Scholar]
  19. Kiyono H, Fukuyama S. 19.  2004. NALT- versus Peyer's-patch-mediated mucosal immunity. Nat. Rev. Immunol. 4:699–710 [Google Scholar]
  20. Obata T, Goto Y, Kunisawa J, Sato S, Sakamoto M. 20.  et al. 2010. Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis. PNAS 107:7419–24 [Google Scholar]
  21. Fung TC, Bessman NJ, Hepworth MR, Kumar N, Shibata N. 21.  et al. 2016. Lymphoid-tissue-resident commensal bacteria promote members of the IL10 cytokine family to establish mutualism. Immunity 44:634–46 [Google Scholar]
  22. Kurashima Y, Goto Y, Kiyono H. 22.  2013. Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation. Eur. J. Immunol. 43:3108–15 [Google Scholar]
  23. Kunisawa J, Kiyono H. 23.  2012. Alcaligenes is commensal bacteria habituating in the gut-associated lymphoid tissue for the regulation of intestinal IgA responses. Front. Immunol. 3:65 [Google Scholar]
  24. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L. 24.  et al. 2005. Diversity of the human intestinal microbial flora. Science 308:1635–38 [Google Scholar]
  25. Atuma C, Strugala V, Allen A, Holm L. 25.  2001. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am. J. Physiol. Gastrointest. Liver Physiol. 280:G922–29 [Google Scholar]
  26. Macpherson AJ, Geuking MB, McCoy KD. 26.  2011. Immunoglobulin A: a bridge between innate and adaptive immunity. Curr. Opin. Gastroenterol. 27:529–33 [Google Scholar]
  27. Noah TK, Donahue B, Shroyer NF. 27.  2011. Intestinal development and differentiation. Exp. Cell Res. 317:2702–10 [Google Scholar]
  28. Barrett JC, Lee JC, Lees CW, Prescott NJ. 28. UK IBD Genet. Consort. et al. 2009. Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nat. Genet 41:1330–34 [Google Scholar]
  29. Van der Sluis M, De Koning BA, De Bruijn AC, Velcich A, Meijerink JP. 29.  et al. 2006. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131:117–29 [Google Scholar]
  30. Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL. 30.  et al. 2010. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42:1118–25 [Google Scholar]
  31. Yang Q, Bermingham NA, Finegold MJ, Zoghbi HY. 31.  2001. Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science 294:2155–58 [Google Scholar]
  32. VanDussen KL, Samuelson LC. 32.  2010. Mouse atonal homolog 1 directs intestinal progenitors to secretory cell rather than absorptive cell fate. Dev. Biol. 346:215–23 [Google Scholar]
  33. Cario E, Gerken G, Podolsky DK. 33.  2004. Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 127:224–38 [Google Scholar]
  34. Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. 34.  2000. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 118:1001–11 [Google Scholar]
  35. Vetrano S, Rescigno M, Cera MR, Correale C, Rumio C. 35.  et al. 2008. Unique role of junctional adhesion molecule-A in maintaining mucosal homeostasis in inflammatory bowel disease. Gastroenterology 135:173–84 [Google Scholar]
  36. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G. 36.  et al. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2:361–67 [Google Scholar]
  37. Turner JR, Rill BK, Carlson SL, Carnes D, Kerner R. 37.  et al. 1997. Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am. J. Physiol. 273:C1378–85 [Google Scholar]
  38. Shen L, Black ED, Witkowski ED, Lencer WI, Guerriero V. 38.  et al. 2006. Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. J. Cell Sci. 119:2095–106 [Google Scholar]
  39. Banan A, Fields JZ, Zhang Y, Keshavarzian A. 39.  2001. Key role of PKC and Ca2+ in EGF protection of microtubules and intestinal barrier against oxidants. Am. J. Physiol. Gastrointest. Liver Physiol. 280:G828–43 [Google Scholar]
  40. Song JC, Hanson CM, Tsai V, Farokhzad OC, Lotz M. 40.  et al. 2001. Regulation of epithelial transport and barrier function by distinct protein kinase C isoforms. Am. J. Physiol. Cell. Physiol. 281:C649–61 [Google Scholar]
  41. Kong J, Zhang Z, Musch MW, Ning G, Sun J. 41.  et al. 2008. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am. J. Physiol. Gastrointest. Liver Physiol. 294:G208–16 [Google Scholar]
  42. Pruteanu M, Hyland NP, Clarke DJ, Kiely B, Shanahan F. 42.  2011. Degradation of the extracellular matrix components by bacterial-derived metalloproteases: implications for inflammatory bowel diseases. Inflamm. Bowel Dis. 17:1189–200 [Google Scholar]
  43. Pruteanu M, Shanahan F. 43.  2013. Digestion of epithelial tight junction proteins by the commensal Clostridium perfringens.. Am. J. Physiol. Gastrointest. Liver Physiol. 305:G740–48 [Google Scholar]
  44. Grill JI, Neumann J, Hiltwein F, Kolligs FT, Schneider MR. 44.  2015. Intestinal E-cadherin deficiency aggravates dextran sodium sulfate-induced colitis. Dig. Dis. Sci. 60:895–902 [Google Scholar]
  45. Karecla PI, Bowden SJ, Green SJ, Kilshaw PJ. 45.  1995. Recognition of E-cadherin on epithelial cells by the mucosal T cell integrin αM290β7 (αEβ7). Eur. J. Immunol. 25:852–56 [Google Scholar]
  46. Cheroutre H, Lambolez F, Mucida D. 46.  2011. The light and dark sides of intestinal intraepithelial lymphocytes. Nat. Rev. Immunol. 11:445–56 [Google Scholar]
  47. Dalton JE, Cruickshank SM, Egan CE, Mears R, Newton DJ. 47.  et al. 2006. Intraepithelial γδ+ lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection. Gastroenterology 131:818–29 [Google Scholar]
  48. Edelblum KL, Singh G, Odenwald MA, Lingaraju A, El Bissati K. 48.  et al. 2015. γδ intraepithelial lymphocyte migration limits transepithelial pathogen invasion and systemic disease in mice. Gastroenterology 148:1417–26 [Google Scholar]
  49. Swamy M, Abeler-Dorner L, Chettle J, Mahlakoiv T, Goubau D. 49.  et al. 2015. Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance. Nat. Commun. 6:7090 [Google Scholar]
  50. Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R. 50.  2002. Protection of the intestinal mucosa by intraepithelial gamma delta T cells. PNAS 99:14338–43 [Google Scholar]
  51. Meehan TF, Witherden DA, Kim CH, Sendaydiego K, Ye I, Garijo O. 51.  et al. 2014. Protection against colitis by CD100-dependent modulation of intraepithelial γδ T lymphocyte function. Mucosal. Immunol. 7:134–42 [Google Scholar]
  52. Birchenough GM, Johansson ME, Gustafsson JK, Bergstrom JH, Hansson GC. 52.  2015. New developments in goblet cell mucus secretion and function. Mucosal. Immunol. 8:712–19 [Google Scholar]
  53. Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L. 53.  et al. 2008. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. PNAS 105:15064–69 [Google Scholar]
  54. Allen A, Hutton DA, Pearson JP. 54.  1998. The MUC2 gene product: a human intestinal mucin. Int. J. Biochem. Cell Biol. 30:797–801 [Google Scholar]
  55. Velcich A, Yang W, Heyer J, Fragale A, Nicholas C. 55.  et al. 2002. Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295:1726–29 [Google Scholar]
  56. Cobo ER, Kissoon-Singh V, Moreau F, Chadee K. 56.  2015. Colonic MUC2 mucin regulates the expression and antimicrobial activity of beta-defensin 2. Mucosal. Immunol. 8:1360–72 [Google Scholar]
  57. Schutte A, Ermund A, Becker-Pauly C, Johansson ME, Rodriguez-Pineiro AM. 57.  et al. 2014. Microbial-induced meprin beta cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus. PNAS 111:12396–401 [Google Scholar]
  58. Mashimo H, Wu DC, Podolsky DK, Fishman MC. 58.  1996. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science 274:262–5 [Google Scholar]
  59. Albert EJ, Marshall JS. 59.  2008. Aging in the absence of TLR2 is associated with reduced IFN-gamma responses in the large intestine and increased severity of induced colitis. J. Leukoc. Biol. 83:833–42 [Google Scholar]
  60. Podolsky DK, Gerken G, Eyking A, Cario E. 60.  2009. Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency. Gastroenterology 137:209–20 [Google Scholar]
  61. Madsen J, Mollenhauer J, Holmskov U. 61.  2010. Review: Gp-340/DMBT1 in mucosal innate immunity. Innate Immun. 16:160–67 [Google Scholar]
  62. Madsen J, Sorensen GL, Nielsen O, Tornoe I, Thim L. 62.  et al. 2013. A variant form of the human deleted in malignant brain tumor 1 (DMBT1) gene shows increased expression in inflammatory bowel diseases and interacts with dimeric trefoil factor 3 (TFF3). PLOS ONE 8:e64441 [Google Scholar]
  63. He W, Wang ML, Jiang HQ, Steppan CM, Shin ME. 63.  et al. 2003. Bacterial colonization leads to the colonic secretion of RELMβ/FIZZ2, a novel goblet cell-specific protein. Gastroenterology 125:1388–97 [Google Scholar]
  64. Artis D, Wang ML, Keilbaugh SA, He W, Brenes M. 64.  et al. 2004. RELMβ/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract. PNAS 101:13596–600 [Google Scholar]
  65. Townsend JM, Fallon GP, Matthews JD, Smith P, Jolin EH. 65.  et al. 2000. IL9-deficient mice establish fundamental roles for IL9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity 13:573–83 [Google Scholar]
  66. Park KS, Korfhagen TR, Bruno MD, Kitzmiller JA, Wan H. 66.  et al. 2007. SPDEF regulates goblet cell hyperplasia in the airway epithelium. J. Clin. Investig. 117:978–88 [Google Scholar]
  67. Oeser K, Schwartz C, Voehringer D. 67.  2015. Conditional IL4/IL13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths. Mucosal. Immunol. 8:672–82 [Google Scholar]
  68. von Moltke J, Ji M, Liang HE, Locksley RM. 68.  2016. Tuft-cell-derived IL25 regulates an intestinal ILC2-epithelial response circuit. Nature 529:221–25 [Google Scholar]
  69. Chen CY, Lee JB, Liu B, Ohta S, Wang PY. 69.  et al. 2015. Induction of interleukin-9-producing mucosal mast cells promotes susceptibility to IgE-mediated experimental food allergy. Immunity 43:788–802 [Google Scholar]
  70. Turner JE, Stockinger B, Helmby H. 70.  2013. IL22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth infection. PLOS Pathog 9:e1003698 [Google Scholar]
  71. Steenwinckel V, Louahed J, Lemaire MM, Sommereyns C, Warnier G. 71.  et al. 2009. IL9 promotes IL13-dependent Paneth cell hyperplasia and up-regulation of innate immunity mediators in intestinal mucosa. J. Immunol. 182:4737–43 [Google Scholar]
  72. McCauley HA, Liu CY, Attia AC, Wikenheiser-Brokamp KA, Zhang Y. 72.  et al. 2014. TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium. Development 141:4628–39 [Google Scholar]
  73. Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP. 73.  et al. 2014. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156:1045–59 [Google Scholar]
  74. Chen GY, Liu M, Wang F, Bertin J, Nunez G. 74.  2011. A functional role for Nlrp6 in intestinal inflammation and tumorigenesis. J. Immunol. 186:7187–94 [Google Scholar]
  75. Normand S, Delanoye-Crespin A, Bressenot A, Huot L, Grandjean T. 75.  et al. 2011. Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls epithelial self-renewal and colorectal carcinogenesis upon injury. PNAS 108:9601–6 [Google Scholar]
  76. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA. 76.  et al. 2011. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145:745–57 [Google Scholar]
  77. Levy M, Thaiss CA, Zeevi D, Dohnalova L, Zilberman-Schapira G. 77.  et al. 2015. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163:1428–43 [Google Scholar]
  78. Nowarski R, Jackson R, Gagliani N, de Zoete MR, Palm NW. 78.  et al. 2015. Epithelial IL18 equilibrium controls barrier function in colitis. Cell 163:1444–56 [Google Scholar]
  79. McDole JR, Wheeler LW, McDonald KG, Wang B, Konjufca V. 79.  et al. 2012. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483:345–49 [Google Scholar]
  80. Knoop KA, McDonald KG, McCrate S, McDole JR, Newberry RD. 80.  2015. Microbial sensing by goblet cells controls immune surveillance of luminal antigens in the colon. Mucosal Immunol 8:198–210 [Google Scholar]
  81. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG. 81.  et al. 2011. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469:415–18 [Google Scholar]
  82. Underwood MA. 82.  2012. Paneth cells and necrotizing enterocolitis. Gut Microbes 3:562–65 [Google Scholar]
  83. van der Flier LG, Clevers H. 83.  2009. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu. Rev. Physiol. 71:241–60 [Google Scholar]
  84. Gregorieff A, Stange DE, Kujala P, Begthel H, van den Born M. 84.  et al. 2009. The Ets-domain transcription factor Spdef promotes maturation of goblet and Paneth cells in the intestinal epithelium. Gastroenterology 137:1333–45e3 [Google Scholar]
  85. Shroyer NF, Wallis D, Venken KJ, Bellen HJ, Zoghbi HY. 85.  2005. Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation. Genes Dev 19:2412–17 [Google Scholar]
  86. Bjerknes M, Cheng H. 86.  2010. Cell Lineage metastability in Gfi1-deficient mouse intestinal epithelium. Dev. Biol. 345:49–63 [Google Scholar]
  87. Mori-Akiyama Y, van den Born M, van Es JH, Hamilton SR, Adams HP. 87.  et al. 2007. SOX9 is required for the differentiation of Paneth cells in the intestinal epithelium. Gastroenterology 133:539–46 [Google Scholar]
  88. Schroeder BO, Ehmann D, Precht JC, Castillo PA, Kuchler R. 88.  et al. 2015. Paneth cell alpha-defensin 6 (HD-6) is an antimicrobial peptide. Mucosal Immunol 8:661–71 [Google Scholar]
  89. Jones DE, Bevins CL. 89.  1992. Paneth cells of the human small intestine express an antimicrobial peptide gene. J. Biol. Chem. 267:23216–25 [Google Scholar]
  90. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME. 90.  et al. 2000. Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1:113–18 [Google Scholar]
  91. Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A. 91.  et al. 2003. Crohn's disease and the NOD2 gene: a role for Paneth cells. Gastroenterology 125:47–57 [Google Scholar]
  92. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP. 92.  et al. 2001. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411:599–603 [Google Scholar]
  93. Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M. 93.  et al. 2005. Reduced Paneth cell α-defensins in ileal Crohn's disease. PNAS 102:18129–34 [Google Scholar]
  94. Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS. 94.  et al. 1999. Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286:113–17 [Google Scholar]
  95. Chu H, Pazgier M, Jung G, Nuccio SP, Castillo PA. 95.  et al. 2012. Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science 337:477–81 [Google Scholar]
  96. Vaishnava S, Behrendt CL, Ismail AS, Eckmann L, Hooper LV. 96.  2008. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. PNAS 105:20858–63 [Google Scholar]
  97. Vaishnava S, Yamamoto M, Severson KM, Ruhn KA, Yu X. 97.  et al. 2011. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334:255–58 [Google Scholar]
  98. Elphick DA, Mahida YR. 98.  2005. Paneth cells: their role in innate immunity and inflammatory disease. Gut 54:1802–9 [Google Scholar]
  99. Ganz T. 99.  2004. Antimicrobial polypeptides. J. Leukoc. Biol. 75:34–38 [Google Scholar]
  100. Qu XD, Lloyd KC, Walsh JH, Lehrer RI. 100.  1996. Secretion of type II phospholipase A2 and cryptdin by rat small intestinal Paneth cells. Infect. Immun. 64:5161–65 [Google Scholar]
  101. Laine VJ, Grass DS, Nevalainen TJ. 101.  2000. Resistance of transgenic mice expressing human group II phospholipase A2 to Escherichia coli infection. Infect. Immun. 68:87–92 [Google Scholar]
  102. Foreman-Wykert AK, Weinrauch Y, Elsbach P, Weiss J. 102.  1999. Cell-wall determinants of the bactericidal action of group IIA phospholipase A2 against gram-positive bacteria. J. Clin. Investig. 103:715–21 [Google Scholar]
  103. Cani PD, Everard A, Duparc T. 103.  2013. Gut microbiota, enteroendocrine functions and metabolism. Curr. Opin. Pharmacol. 13:935–40 [Google Scholar]
  104. Gribble FM, Reimann F. 104.  2016. Enteroendocrine cells: chemosensors in the intestinal epithelium. Annu. Rev. Physiol. 78:277–99 [Google Scholar]
  105. Jenny M, Uhl C, Roche C, Duluc I, Guillermin V. 105.  et al. 2002. Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium. EMBO J 21:6338–47 [Google Scholar]
  106. Mellitzer G, Beucher A, Lobstein V, Michel P, Robine S. 106.  et al. 2010. Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival. J. Clin. Investig. 120:1708–21 [Google Scholar]
  107. Marathe CS, Rayner CK, Jones KL, Horowitz M. 107.  2013. Glucagon-like peptides 1 and 2 in health and disease: a review. Peptides 44:75–86 [Google Scholar]
  108. Drucker DJ, Erlich P, Asa SL, Brubaker PL. 108.  1996. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. PNAS 93:7911–16 [Google Scholar]
  109. Van Landeghem L, Santoro MA, Mah AT, Krebs AE, Dehmer JJ. 109.  et al. 2015. IGF1 stimulates crypt expansion via differential activation of 2 intestinal stem cell populations. FASEB J 29:2828–42 [Google Scholar]
  110. Bortvedt SF, Lund PK. 110.  2012. Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors. Curr. Opin. Gastroenterol. 28:89–98 [Google Scholar]
  111. Nagatake T, Fujita H, Minato N, Hamazaki Y. 111.  2014. Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine. PLOS ONE 9:e90638 [Google Scholar]
  112. Petersen N, Reimann F, Bartfeld S, Farin HF, Ringnalda FC. 112.  et al. 2014. Generation of L cells in mouse and human small intestine organoids. Diabetes 63:410–20 [Google Scholar]
  113. Nohr MK, Pedersen MH, Gille A, Egerod KL, Engelstoft MS. 113.  et al. 2013. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells versus FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology 154:3552–64 [Google Scholar]
  114. Liddle RA. 114.  1997. Cholecystokinin cells. Annu. Rev. Physiol. 59:221–42 [Google Scholar]
  115. McDermott JR, Leslie FC, D'Amato M, Thompson DG, Grencis RK. 115.  et al. 2006. Immune control of food intake: Enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation. Gut 55:492–97 [Google Scholar]
  116. Worthington JJ. 116.  2015. The intestinal immunoendocrine axis: novel cross-talk between enteroendocrine cells and the immune system during infection and inflammatory disease. Biochem. Soc. Trans. 43:727–33 [Google Scholar]
  117. Gerbe F, Legraverend C, Jay P. 117.  2012. The intestinal epithelium tuft cells: specification and function. Cell Mol. Life Sci. 69:2907–17 [Google Scholar]
  118. Gerbe F, van Es JH, Makrini L, Brulin B, Mellitzer G. 118.  et al. 2011. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium. J. Cell Biol. 192:767–80 [Google Scholar]
  119. Matsumoto I, Ohmoto M, Narukawa M, Yoshihara Y, Abe K. 119.  2011. Skn-1a (Pou2f3) specifies taste receptor cell lineage. Nat. Neurosci. 14:685–87 [Google Scholar]
  120. Gerbe F, Sidot E, Smyth DJ, Ohmoto M, Matsumoto I. 120.  et al. 2016. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529:226–30 [Google Scholar]
  121. Howitt MR, Lavoie S, Michaud M, Blum AM, Tran SV. 121.  et al. 2016. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351:1329–33 [Google Scholar]
  122. Mabbott NA, Donaldson DS, Ohno H, Williams IR, Mahajan A. 122.  2013. Microfold (M) cells: Important immunosurveillance posts in the intestinal epithelium. Mucosal Immunol 6:666–77 [Google Scholar]
  123. Nochi T, Yuki Y, Matsumura A, Mejima M, Terahara K. 123.  et al. 2007. A novel M cell-specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses. J. Exp. Med. 204:2789–96 [Google Scholar]
  124. Terahara K, Yoshida M, Igarashi O, Nochi T, Pontes GS. 124.  et al. 2008. Comprehensive gene expression profiling of Peyer's patch M cells, villous M-like cells, and intestinal epithelial cells. J. Immunol. 180:7840–46 [Google Scholar]
  125. Clark MA, Hirst BH, Jepson MA. 125.  1998. M-cell surface β1 integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer's patch M cells. Infect. Immun. 66:1237–43 [Google Scholar]
  126. Hase K, Ohshima S, Kawano K, Hashimoto N, Matsumoto K. 126.  et al. 2005. Distinct gene expression profiles characterize cellular phenotypes of follicle-associated epithelium and M cells. DNA Res 12:127–37 [Google Scholar]
  127. Kim SH, Jung DI, Yang IY, Kim J, Lee KY. 127.  et al. 2011. M cells expressing the complement C5a receptor are efficient targets for mucosal vaccine delivery. Eur. J. Immunol. 41:3219–29 [Google Scholar]
  128. Iwasaki A, Welker R, Mueller S, Linehan M, Nomoto A. 128.  et al. 2002. Immunofluorescence analysis of poliovirus receptor expression in Peyer's patches of humans, primates, and CD155 transgenic mice: implications for poliovirus infection. J. Infect. Dis. 186:585–92 [Google Scholar]
  129. Freedman SD, Kern HF, Scheele GA. 129.  1998. Cleavage of GPI-anchored proteins from the plasma membrane activates apical endocytosis in pancreatic acinar cells. Eur. J. Cell Biol. 75:163–73 [Google Scholar]
  130. Hase K, Kawano K, Nochi T, Pontes GS, Fukuda S. 130.  et al. 2009. Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response. Nature 462:226–30 [Google Scholar]
  131. Mulvey MA. 131.  2002. Adhesion and entry of uropathogenic Escherichia coli.. Cell Microbiol. 4:257–71 [Google Scholar]
  132. Lelouard H, Fallet M, de Bovis B, Meresse S, Gorvel JP. 132.  2012. Peyer's patch dendritic cells sample antigens by extending dendrites through M cell-specific transcellular pores. Gastroenterology 142:592–601e3 [Google Scholar]
  133. Reboldi A, Cyster JG. 133.  2016. Peyer's patches: organizing B-cell responses at the intestinal frontier. Immunol. Rev. 271:230–45 [Google Scholar]
  134. Hase K, Murakami T, Takatsu H, Shimaoka T, Iimura M. 134.  et al. 2006. The membrane-bound chemokine CXCL16 expressed on follicle-associated epithelium and M cells mediates lympho-epithelial interaction in GALT. J. Immunol. 176:43–51 [Google Scholar]
  135. Lugering A, Floer M, Westphal S, Maaser C, Spahn TW. 135.  et al. 2005. Absence of CCR6 inhibits CD4+ regulatory T-cell development and M-cell formation inside Peyer's patches. Am. J. Pathol. 166:1647–54 [Google Scholar]
  136. Westphal S, Lugering A, von Wedel J, von Eiff C, Maaser C. 136.  et al. 2008. Resistance of chemokine receptor 6-deficient mice to Yersinia enterocolitica infection: evidence of defective M-cell formation in vivo. Am. J. Pathol. 172:671–80 [Google Scholar]
  137. Ebisawa M, Hase K, Takahashi D, Kitamura H, Knoop KA. 137.  et al. 2011. CCR6hiCD11cint B cells promote M-cell differentiation in Peyer's patch. Int. Immunol. 23:261–69 [Google Scholar]
  138. Kerneis S, Bogdanova A, Kraehenbuhl JP, Pringault E. 138.  1997. Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria. Science 277:949–52 [Google Scholar]
  139. Plaut AG. 139.  1983. The IgA1 proteases of pathogenic bacteria. Annu. Rev. Microbiol. 37:603–22 [Google Scholar]
  140. Rochereau N, Drocourt D, Perouzel E, Pavot V, Redelinghuys P. 140.  et al. 2013. Dectin-1 is essential for reverse transcytosis of glycosylated SIgA-antigen complexes by intestinal M cells. PLOS Biol 11:e1001658 [Google Scholar]
  141. Rochereau N, Pavot V, Verrier B, Ensinas A, Genin C. 141.  et al. 2015. Secretory IgA as a vaccine carrier for delivery of HIV antigen to M cells. Eur. J. Immunol. 45:773–79 [Google Scholar]
  142. Shima H, Watanabe T, Fukuda S, Fukuoka S, Ohara O. 142.  et al. 2014. A novel mucosal vaccine targeting Peyer's patch M cells induces protective antigen-specific IgA responses. Int. Immunol. 26:619–25 [Google Scholar]
  143. Hanazato M, Nakato G, Nishikawa F, Hase K, Nishikawa S. 143.  et al. 2014. Selection of an aptamer against mouse GP2 by SELEX. Cell Struct. Funct. 39:23–29 [Google Scholar]
  144. Knoop KA, Kumar N, Butler BR, Sakthivel SK, Taylor RT. 144.  et al. 2009. RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium. J. Immunol. 183:5738–47 [Google Scholar]
  145. Wood MB, Rios D, Williams IR. 145.  2016. TNF-α augments RANKL-dependent intestinal M cell differentiation in enteroid cultures. Am. J. Physiol. Cell Physiol. 311:C498–507 [Google Scholar]
  146. Kanaya T, Hase K, Takahashi D, Fukuda S, Hoshino K. 146.  et al. 2012. The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells. Nat. Immunol. 13:729–36 [Google Scholar]
  147. de Lau W, Kujala P, Schneeberger K, Middendorp S, Li VS. 147.  et al. 2012. Peyer's patch M cells derived from Lgr5+ stem cells require SpiB and are induced by RankL in cultured “miniguts. ”. Mol. Cell Biol. 32:3639–47 [Google Scholar]
  148. Sato S, Kaneto S, Shibata N, Takahashi Y, Okura H. 148.  et al. 2013. Transcription factor Spi-B-dependent and -independent pathways for the development of Peyer's patch M cells. Mucosal Immunol 6:838–46 [Google Scholar]
  149. Hsieh EH, Fernandez X, Wang J, Hamer M, Calvillo S. 149.  et al. 2010. CD137 is required for M cell functional maturation but not lineage commitment. Am. J. Pathol. 177:666–76 [Google Scholar]
  150. Okumura R, Kurakawa T, Nakano T, Kayama H, Kinoshita M. 150.  et al. 2016. Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. Nature 532:117–21 [Google Scholar]
  151. Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA. 151.  et al. 2012. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336:1321–25 [Google Scholar]
  152. Upadhyay V, Poroyko V, Kim TJ, Devkota S, Fu S. 152.  et al. 2012. Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nat. Immunol. 13:947–53 [Google Scholar]
  153. Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II. 153.  et al. 2014. Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Science 345:1254009 [Google Scholar]
  154. Pickard JM, Maurice CF, Kinnebrew MA, Abt MC, Schenten D. 154.  et al. 2014. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness. Nature 514:638–41 [Google Scholar]
  155. Lin B, Saito M, Sakakibara Y, Hayashi Y, Yanagisawa M. 155.  et al. 2001. Characterization of three members of murine α1,2-fucosyltransferases: change in the expression of the Se gene in the intestine of mice after administration of microbes. Arch. Biochem. Biophys. 388:207–15 [Google Scholar]
  156. Iwamori M, Domino SE. 156.  2004. Tissue-specific loss of fucosylated glycolipids in mice with targeted deletion of α(1,2)fucosyltransferase genes. Biochem. J. 380:75–81 [Google Scholar]
  157. Domino SE, Hiraiwa N, Lowe JB. 157.  1997. Molecular cloning, chromosomal assignment and tissue-specific expression of a murine α(1,2)fucosyltransferase expressed in thymic and epididymal epithelial cells. Biochem. J. 327:Part 1105–15 [Google Scholar]
  158. Terahara K, Nochi T, Yoshida M, Takahashi Y, Goto Y. 158.  et al. 2011. Distinct fucosylation of M cells and epithelial cells by Fut1 and Fut2, respectively, in response to intestinal environmental stress. Biochem. Biophys. Res. Commun. 404:822–28 [Google Scholar]
  159. Hooper LV, Xu J, Falk PG, Midtvedt T, Gordon JI. 159.  1999. A molecular sensor that allows a gut commensal to control its nutrient foundation in a competitive ecosystem. PNAS 96:9833–38 [Google Scholar]
  160. Rodriguez-Diaz J, Monedero V, Yebra MJ. 160.  2011. Utilization of natural fucosylated oligosaccharides by three novel α-l-fucosidases from a probiotic Lactobacillus casei strain. Appl. Environ. Microbiol. 77:703–5 [Google Scholar]
  161. Becerra JE, Yebra MJ, Monedero V. 161.  2015. An l-fucose operon in the probiotic Lactobacillus rhamnosus GG is involved in adaptation to gastrointestinal conditions. Appl. Environ. Microbiol. 81:3880–88 [Google Scholar]
  162. Rodriguez-Diaz J, Carbajo RJ, Pineda-Lucena A, Monedero V, Yebra MJ. 162.  2013. Synthesis of fucosyl-n-acetylglucosamine disaccharides by transfucosylation using α-l-fucosidases from Lactobacillus casei.. Appl. Environ. Microbiol. 79:3847–50 [Google Scholar]
  163. Pham TA, Clare S, Goulding D, Arasteh JM, Stares MD. 163.  et al. 2014. Epithelial IL22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen. Cell Host Microbe 16:504–16 [Google Scholar]
  164. Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y. 164.  et al. 2015. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:367–80 [Google Scholar]
  165. Tong M, McHardy I, Ruegger P, Goudarzi M, Kashyap PC. 165.  et al. 2014. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism. ISME J 8:2193–206 [Google Scholar]
  166. Wacklin P, Makivuokko H, Alakulppi N, Nikkila J, Tenkanen H. 166.  et al. 2011. Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine. PLOS ONE 6:e20113 [Google Scholar]
  167. McGovern DP, Jones MR, Taylor KD, Marciante K, Yan X. 167.  et al. 2010. Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. Hum. Mol. Genet. 19:3468–76 [Google Scholar]
  168. Folseraas T, Melum E, Rausch P, Juran BD, Ellinghaus E. 168.  et al. 2012. Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. J. Hepatol. 57:366–75 [Google Scholar]
  169. Hazra A, Kraft P, Selhub J, Giovannucci EL, Thomas G. 169.  et al. 2008. Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat. Genet. 40:1160–62 [Google Scholar]
  170. Goto Y, Lamichhane A, Kamioka M, Sato S, Honda K. 170.  et al. 2015. IL10-producing CD4+ T cells negatively regulate fucosylation of epithelial cells in the gut. Sci. Rep. 5:15918 [Google Scholar]
  171. Rieder F, Brenmoehl J, Leeb S, Scholmerich J, Rogler G. 171.  2007. Wound healing and fibrosis in intestinal disease. Gut 56:130–39 [Google Scholar]
  172. Ding S, Walton KL, Blue RE, McNaughton K, Magness ST. 172.  et al. 2012. Mucosal healing and fibrosis after acute or chronic inflammation in wild type FVB-N mice and C57BL6 procollagen α1(I)-promoter-GFP reporter mice. PLOS ONE 7:e42568 [Google Scholar]
  173. Roulis M, Flavell RA. 173.  2016. Fibroblasts and myofibroblasts of the intestinal lamina propria in physiology and disease. Differentiation 92:116–31 [Google Scholar]
  174. Sturm A, Dignass AU. 174.  2008. Epithelial restitution and wound healing in inflammatory bowel disease. World J. Gastroenterol. 14:348–53 [Google Scholar]
  175. Neurath MF. 175.  2014. New targets for mucosal healing and therapy in inflammatory bowel diseases. Mucosal. Immunol. 7:6–19 [Google Scholar]
  176. Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada JI. 176.  et al. 1999. Myofibroblasts. I. Paracrine cells important in health and disease. Am. J. Physiol. 277:C1–9 [Google Scholar]
  177. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. 177.  1993. Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J. Cell Biol. 122:103–11 [Google Scholar]
  178. Islam MS, Kusakabe M, Horiguchi K, Iino S, Nakamura T. 178.  et al. 2014. PDGF and TGF-β promote tenascin-C expression in subepithelial myofibroblasts and contribute to intestinal mucosal protection in mice. Br. J. Pharmacol. 171:375–88 [Google Scholar]
  179. Song X, Dai D, He X, Zhu S, Yao Y. 179.  et al. 2015. Growth factor FGF2 cooperates with interleukin-17 to repair intestinal epithelial damage. Immunity 43:488–501 [Google Scholar]
  180. Miyoshi H, Ajima R, Luo CT, Yamaguchi TP, Stappenbeck TS. 180.  2012. Wnt5a potentiates TGF-β signaling to promote colonic crypt regeneration after tissue injury. Science 338:108–13 [Google Scholar]
  181. Valenta T, Degirmenci B, Moor AE, Herr P, Zimmerli D. 181.  et al. 2016. Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis. Cell Rep 15:911–18 [Google Scholar]
  182. Mahapatro M, Foersch S, Hefele M, He G-W, Giner-Ventura E. 182.  et al. 2016. Programming of intestinal epithelial differentiation by IL-33 derived from pericryptal fibroblasts in response to systemic infection. Cell Rep 15:1743–56 [Google Scholar]
  183. Aparicio-Domingo P, Romera-Hernandez M, Karrich JJ, Cornelissen F, Papazian N. 183.  et al. 2015. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage. J. Exp. Med. 212:1783–91 [Google Scholar]
  184. Monticelli LA, Osborne LC, Noti M, Tran SV, Zaiss DM. 184.  et al. 2015. IL33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. PNAS 112:10762–67 [Google Scholar]
  185. Yan F, Cao H, Cover TL, Washington MK, Shi Y. 185.  et al. 2011. Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism. J. Clin. Investig. 121:2242–53 [Google Scholar]
  186. Scheibe K, Backert I, Wirtz S, Hueber A, Schett G. 186.  et al. 2016. IL36R signalling activates intestinal epithelial cells and fibroblasts and promotes mucosal healing in vivo. Gut In press. doi: 10.1136/gutjnl-2015-310374 [Google Scholar]
  187. Takahashi K, Nishida A, Shioya M, Imaeda H, Bamba S. 187.  et al. 2015. IL-1beta is a strong inducer of IL36γ expression in human colonic myofibroblasts. PLOS ONE 10:e0138423 [Google Scholar]
  188. Egea L, McAllister CS, Lakhdari O, Minev I, Shenouda S. 188.  et al. 2013. GM-CSF produced by nonhematopoietic cells is required for early epithelial cell proliferation and repair of injured colonic mucosa. J. Immunol. 190:1702–13 [Google Scholar]
  189. Choi JS, Kim KH, Lau LF. 189.  2015. The matricellular protein CCN1 promotes mucosal healing in murine colitis through IL6. Mucosal Immunol 8:1285–96 [Google Scholar]
  190. Driskell RR, Watt FM. 190.  2015. Understanding fibroblast heterogeneity in the skin. Trends Cell Biol 25:92–99 [Google Scholar]
  191. Kurashima Y, Amiya T, Fujisawa K, Shibata N, Suzuki Y. 191.  et al. 2014. The enzyme Cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis. Immunity 40:530–41 [Google Scholar]
  192. Peloquin JM, Goel G, Villablanca EJ, Xavier RJ. 192.  2016. Mechanisms of pediatric inflammatory bowel disease. Annu. Rev. Immunol. 34:31–64 [Google Scholar]
  193. Wesemann DR, Nagler CR. 193.  2016. The microbiome, timing, and barrier function in the context of allergic disease. Immunity 44:728–38 [Google Scholar]
  194. Fritz JH, Rojas OL, Simard N, McCarthy DD, Hapfelmeier S. 194.  et al. 2012. Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut. Nature 481:199–203 [Google Scholar]
  195. Vicente-Suarez I, Larange A, Reardon C, Matho M, Feau S. 195.  et al. 2015. Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells. Mucosal Immunol 8:141–51 [Google Scholar]
  196. Wick G, Grundtman C, Mayerl C, Wimpissinger TF, Feichtinger J. 196.  et al. 2013. The immunology of fibrosis. Annu. Rev. Immunol. 31:107–35 [Google Scholar]
  197. Sipos F, Galamb O. 197.  2012. Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions in the colon. World J. Gastroenterol. 18:601–8 [Google Scholar]
  198. Atkinson S, Williams P. 198.  2009. Quorum sensing and social networking in the microbial world. J. R. Soc. Interface 6:959–78 [Google Scholar]
  199. Sansonetti PJ. 199.  2011. To be or not to be a pathogen: That is the mucosally relevant question. Mucosal. Immunol. 4:8–14 [Google Scholar]
  200. Fujiya M, Musch MW, Nakagawa Y, Hu S, Alverdy J. 200.  et al. 2007. The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host Microbe 1:299–308 [Google Scholar]
/content/journals/10.1146/annurev-immunol-051116-052424
Loading
/content/journals/10.1146/annurev-immunol-051116-052424
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error