The mucosal immune system at the gastrointestinal barrier

Best Practice and Research: Clinical Gastroenterology

Volumn 22, Issue 3, 2008, Pages 391-409

  Schenk, Mirjam ^a,b   Mueller, Christoph ^a  

^a UNIVERSITY OF BERN   (Switzerland)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

adaptive immunity; immunological ignorance; innate immunity; intestinal barrier; intestinal tolerance

Indexed keywords

ALPHA DEFENSIN; ANTIGEN; B7 ANTIGEN; CATHELICIDIN; CD11B ANTIGEN; CD14 ANTIGEN; CD33 ANTIGEN; CD4 ANTIGEN; CD40 ANTIGEN; CD68 ANTIGEN; CD86 ANTIGEN; CD8ALPHA ANTIGEN; CHEMOTACTIC FACTOR; EPITHELIAL DERIVED NEUTROPHIL ACTIVATING FACTOR 78; HLA DR ANTIGEN; IMMUNOGLOBULIN E; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; LYSOZYME; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MATRILYSIN; MICROSOMAL AMINOPEPTIDASE; TOLL LIKE RECEPTOR 4; TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 1; TUMOR NECROSIS FACTOR;

ADAPTIVE IMMUNITY; ANTIGEN EXPRESSION; ARTICLE; CELL INTERACTION; CELL SUBPOPULATION; COMMENSAL; CYTOKINE PRODUCTION; DENDRITIC CELL; DIGESTIVE SYSTEM INFLAMMATION; EFFECTOR CELL; ENTERITIS; FOOD ALLERGY; GASTROINTESTINAL MUCOSA; GASTROINTESTINAL TRACT FUNCTION; GENE MUTATION; GOBLET CELL; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; GRANULOCYTE; HEMATOPOIETIC CELL; HOMEOSTASIS; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOLOGICAL TOLERANCE; INFECTION RESISTANCE; INNATE IMMUNITY; INTESTINE EPITHELIUM; INTESTINE FLORA; INTESTINE MUCOSA PERMEABILITY; MAST CELL; MICROBIAL COLONIZATION; MUCOSAL IMMUNITY; MUCUS; NONHUMAN; OPSONIZATION; PANETH CELL; PHAGOCYTOSIS; PROTEIN SECRETION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; T LYMPHOCYTE SUBPOPULATION;

GASTROINTESTINAL DISEASES; GASTROINTESTINAL TRACT; HUMANS; IMMUNITY, MUCOSAL; MUCOUS MEMBRANE;

EID: 43549117511     PISSN: 15216918     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bpg.2007.11.002     Document Type: Article

References (127)

1. A.J. Macpherson N.L. Harris Interactions between commensal intestinal bacteria and the immune system Nat Rev Immunol 4 6 2004 478 485
2. A.J. Macpherson T. Uhr Compartmentalization of the mucosal immune responses to commensal intestinal bacteria Ann N Y Acad Sci 1029 2004 36 43
3. J.L. Madara S. Nash R. Moore Structure and function of the intestinal epithelial barrier in health and disease Monogr Pathol 31 1990 306 324
4. A. Frey K.T. Giannasca R. Weltzin Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting J Exp Med 184 3 1996 1045 1059
5. A.P. Corfield N. Myerscough R. Longman Mucins and mucosal protection in the gastrointestinal tract: new prospects for mucins in the pathology of gastrointestinal disease Gut 47 4 2000 589 594
6. H.G. Boman Innate immunity and the normal microflora Immunol Rev 173 2000 5 16
7. R.E. Ley D.A. Peterson J.I. Gordon Ecological and evolutionary forces shaping microbial diversity in the human intestine Cell 124 4 2006 837 848
8. L.V. Hooper M.H. Wong A. Thelin Molecular analysis of commensal host-microbial relationships in the intestine Science 291 5505 2001 881 884
9. M.L. Hermiston J.I. Gordon Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-Cadherin Science 270 1995 1203 1207
10. C. Mueller A.J. Macpherson Layers of mutualism with commensal bacteria protect us from intestinal inflammation Gut 55 2 2006 276 284
11. K. Fukushima I. Sasaki H. Ogawa Colonization of microflora in mice: mucosal defense against luminal bacteria J Gastroenterol 34 1 1999 54 60
12. C.L. Wilson A.J. Ouellette D.P. Satchell Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense Science 286 5437 1999 113 117
13. T. Ayabe D.P. Satchell C.L. Wilson Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria Nat Immunol 1 2 2000 113 118
14. W.M. Wong G.W. Stamp G. Elia Proliferative populations in intestinal metaplasia: evidence of deregulation in Paneth and goblet cells, but not endocrine cells J Pathol 190 1 2000 107 113
15. R.N. Cunliffe F.R. Rose J. Keyte Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease Gut 48 2 2001 176 185
16. I. Bjarnason A. Macpherson D. Hollander Intestinal permeability: an overview Gastroenterology 108 5 1995 1566 1581
17. B.L. Kelsall M. Rescigno Mucosal dendritic cells in immunity and inflammation Nat Immunol 5 11 2004 1091 1095
18. J. Rugtveit A. Bakka P. Brandtzaeg Differential distribution of B7.1 (CD80) and B7.2 (CD86) costimulatory molecules on mucosal macrophage subsets in human inflammatory bowel disease (IBD) Clin Exp Immunol 110 1 1997 104 113
19. T. Kanai R. Ilyama T. Ishikura Role of the innate immune system in the development of chronic colitis J Gastroenterol 2002 37 Suppl 14(4): 38-42
20. P. Sansonetti V. Braesco Phagocytosis of bacterial pathogens: implications in the host response Semin Immunol 13 6 2001 381 390
21. C. Varol L. Landsman D.K. Fogg Monocytes give rise to mucosal, but not splenic, conventional dendritic cells J Exp Med 204 1 2007 171 180
22. S. Gordon The macrophage Bioessays 17 11 1995 977 986
23. P.D. Smith C. Ochsenbauer-Jambor L.E. Smythies Intestinal macrophages: unique effector cells of the innate immune system Immunol Rev 206 2005 149 159
24. L.E. Smythies M. Sellers R.H. Clements Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity J Clin Invest 115 1 2005 66 75
25. P.D. Smith L.E. Smythies M. Mosteller-Barnum Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities J Immunol 167 5 2001 2651 2656
26. V.A. Fadok D.L. Bratton A. Konowal Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF J Clin Invest 101 4 1998 890 898
27. W.J. Zhang S.S. Zheng In vitro study of immunosuppressive effect of apoptotic cells J Zhejiang Univ Sci B 6 9 2005 919 925
28. K. Kurosaka N. Watanabe Y. Kobayashi Potentiation by human serum of anti-inflammatory cytokine production by human macrophages in response to apoptotic cells J Leukoc Biol 71 6 2002 950 956
29. F.P. Huang N. Platt M. Wykes A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes J Exp Med 191 3 2000 435 444
30. M. Schenk A. Bouchon S. Birrer Macrophages expressing triggering receptor expressed on myeloid cells-1 are underrepresented in the human intestine J Immunol 174 1 2005 517 524
31. A. Bouchon J. Dietrich M. Colonna Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes J Immunol 164 10 2000 4991 4995
32. D.N. Cook D.M. Prosser R. Forster CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue Immunity 12 5 2000 495 503
33. M. Rescigno M. Urbano B. Valzasina Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria Nat Immunol 2 4 2001 361 367
34. J.H. Niess S. Brand X. Gu CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance Science 307 5707 2005 254 258
35. B.L. Kelsall W. Strober Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer's patch J Exp Med 183 1 1996 237 247
36. A. Iwasaki B.L. Kelsall Unique functions of cd11b(+), CD8alpha(+), and double-negative Peyer's patch dendritic cells J Immunol 166 8 2001 4884 4890
37. J. Bilsborough J.L. Viney Gastrointestinal dendritic cells play a role in immunity, tolerance, and disease Gastroenterology 127 1 2004 300 309
38. L. Mazzucchelli C. Hauser K. Zgraggen Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation Am J Pathol 144 5 1994 997 1007
39. K. Z'Graggen A. Walz L. Mazzucchelli The C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium in inflammatory bowel disease Gastroenterology 113 3 1997 808 816
40. C.N. Serhan J. Savill Resolution of inflammation: the beginning programs the end Nat Immunol 6 12 2005 1191 1197
41. B. Echtenacher D.N. Mannel L. Hultner Critical protective role of mast cells in a model of acute septic peritonitis Nature 381 6577 1996 75 77
42. L.F. Lu E.F. Lind D.C. Gondek Mast cells are essential intermediaries in regulatory T-cell tolerance Nature 442 7106 2006 997 1002
43. S.C. Bischoff S. Kramer Human mast cells, bacteria, and intestinal immunity Immunol Rev 217 2007 329 337
44. A. Straumann H.U. Simon The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract Allergy 59 1 2004 15 25
45. S.P. Hogan A. Mishra E.B. Brandt A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation Nat Immunol 2 4 2001 353 360
46. C. Berlin E.L. Berg M.J. Briskin Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1 Cell 74 1 1993 185
47. T. Dajotoy P. Andersson A. Bjartell Human eosinophils produce the T cell-attracting chemokines MIG and IP-10 upon stimulation with IFN-gamma J Leukoc Biol 76 3 2004 685 691
48. F. Sallusto D. Lenig C.R. Mackay Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes J Exp Med 187 6 1998 875 883
49. D.C. Baumgart S.R. Carding Inflammatory bowel disease: cause and immunobiology Lancet 369 9573 2007 1627 1640
50. C.S. Kaetzel J.K. Robinson K.R. Chintalacharuvu The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA Proc Natl Acad Sci USA 88 19 1991 8796 8800
51. 2: a possible implication for mucosal defense J Immunol 161 10 1998 5445 5453
52. J. Mestecky C. Lue M.W. Russell Selective transport of IgA. Cellular and molecular aspects Gastroenterol Clin North Am 20 3 1991 441 471
53. P. Brandtzaeg F.E. Johansen Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties Immunol Rev 206 2005 32 63
54. P. Brandtzaeg I.N. Farstad G. Haraldsen Regional specialization in the mucosal immune system: primed cells do not always home along the same track Immunol Today 20 6 1999 267 277
55. A. Kallies J. Hasbold D.M. Tarlinton Plasma cell ontogeny defined by quantitative changes in blimp-1 expression J Exp Med 200 8 2004 967 977
56. B. Bartholdy P. Matthias Transcriptional control of B cell development and function Gene 327 1 2004 1 23
57. S.W. Craig J.J. Cebra Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit J Exp Med 134 1 1971 188 200
58. M.R. McDermott J. Bienenstock Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues J Immunol 122 5 1979 1892 1898
59. M. McWilliams J.M. Phillips-Quagliata M.E. Lamm Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis J Exp Med 145 4 1977 866 875
60. D. Guy-Grand C. Griscelli P. Vassalli The gut-associated lymphoid system: nature and properties of the large dividing cells Eur J Immunol 4 6 1974 435 443
61. M.E. Roux M. McWilliams J.M. Phillips-Quagliata Differentiation pathway of Peyer's patch precursors of IgA plasma cells in the secretory immune system Cell Immunol 61 1 1981 141 153
62. A.J. Macpherson D. Gatto E. Sainsbury A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria Science 288 5474 2000 2222 2226
63. M.E. Conley D.L. Delacroix Intravascular and mucosal immunoglobulin A: two separate but related systems of immune defense? Ann Intern Med 106 6 1987 892 899
64. P. Brandtzaeg I.N. Farstad F.E. Johansen The B-cell system of human mucosae and exocrine glands Immunol Rev 171 1999 45 87
65. P.T. Crowe M.N. Marsh Morphometric analysis of intestinal mucosa. VI – Principles in enumerating intra-epithelial lymphocytes Virchows Arch 424 3 1994 301 306
66. F. Le Deist G. de Saint Basile F. Mazerolles Primary membrane T cell immunodeficiencies Clin Immunol Immunopathol 61 2 Pt 2 1991 S56 S60
67. T. Goodman L. Lefranccois Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes Nature 333 6176 1988 855 858
68. + cells Nat Immunol 4 10 2003 991 998
69. D. Guy Grand B. Rocha P. Mintz Different use of T cell receptor transducing modules in two populations of gut intraepithelial lymphocytes are related to distinct pathways of T cell differentiation J Exp Med 180 2 1994 673 679
70. P. Poussier H.S. Teh M. Julius Thymus-independent positive and negative selection of T cells expressing a major histocompatibility complex class I restricted transgenic T cell receptor alpha/beta in the intestinal epithelium J Exp Med 178 1993 1947 1957
71. B. Rocha H. von Boehmer D. Guy-Grand Selection of intraepithelial lymphocytes with CD8 alpha/alpha co-receptors by self-antigen in the murine gut Proc Natl Acad Sci U S A 89 12 1992 5336 5340
72. J. Kunisawa I. Takahashi H. Kiyono Intraepithelial lymphocytes: their shared and divergent immunological behaviors in the small and large intestine Immunol Rev 215 2007 136 153
73. C. Lundqvist S. Melgar M.M. Yeung Intraepithelial lymphocytes in human gut have lytic potential and a cytokine profile that suggest T helper 1 and cytotoxic functions J Immunol 157 5 1996 1926 1934
74. F. Leon E. Roldan L. Sanchez Human small-intestinal epithelium contains functional natural killer lymphocytes Gastroenterology 125 2 2003 345 356
75. A. Chott D. Gerdes A. Spooner Intraepithelial lymphocytes in normal human intestine do not express proteins associated with cytolytic function Am J Pathol 151 2 1997 435 442
76. S. Muller J. Lory N. Corazza Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease Am J Pathol 152 1 1998 261 268
77. R.L. Reinhardt A. Khoruts R. Merica Visualizing the generation of memory CD4 T cells in the whole body Nature 410 6824 2001 101 105
78. S.K. Kim D.S. Reed W.R. Heath Activation and migration of CD8 T cells in the intestinal mucosa J Immunol 159 9 1997 4295 4306
79. S. Muller M. Buhler-Jungo C. Mueller Intestinal intraepithelial lymphocytes exert potent protective cytotoxic activity during an acute virus infection J Immunol 164 4 2000 1986 1994
80. F. Powrie M.W. Leach S. Mauze Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice Int Immunol 5 11 1993 1461 1471
81. P.J. Morrissey K. Charrier S. Braddy CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. Disease development is prevented by cotransfer of purified CD4+ T cells J Exp Med 178 1993 237 244
82. L. Saurer I. Seibold S. Rihs Virus-induced activation of self-specific TCRalphabeta CD8alphaalpha intraepithelial lymphocytes does not abolish their self-tolerance in the intestine J Immunol 172 7 2004 4176 4183
83. P. Poussier T. Ning D. Banerjee A unique subset of self-specific intraintestinal T cells maintains gut integrity J Exp Med 195 11 2002 1491 1497
84. M. Allez L. Mayer Regulatory T cells: peace keepers in the gut Inflamm Bowel Dis 10 5 2004 666 676
85. H. Groux A. O'Garra M. Bigler A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis Nature 389 6652 1997 737 742
86. G. Prioult C. Nagler-Anderson Mucosal immunity and allergic responses: lack of regulation and/or lack of microbial stimulation? Immunol Rev 206 2005 204 218
87. A.M. Mowat L.A. Parker H. Beacock-Sharp Oral tolerance: overview and historical perspectives Ann N Y Acad Sci 1029 2004 1 8
88. K.H. Mills P. McGuirk Antigen-specific regulatory T cells – their induction and role in infection Semin Immunol 16 2 2004 107 117
89. S. Makita T. Kanai S. Oshima CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells J Immunol 173 5 2004 3119 3130
90. S. Hori T. Nomura S. Sakaguchi Control of Regulatory T Cell Development by the transcription factor FOXP3 Science 9 2003 9
91. E.M. Shevach CD4+ CD25+ suppressor T cells: more questions than answers Nat Rev Immunol 2 6 2002 389 400
92. B. Dubois L. Chapat A. Goubier Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation Blood 102 9 2003 3295 3301
93. B. Dubois A. Goubier G. Joubert Oral tolerance and regulation of mucosal immunity Cell Mol Life Sci 62 12 2005 1322 1332
94. J.D. Fontenot A.Y. Rudensky A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3 Nat Immunol 6 4 2005 331 337
95. J.D. Fontenot J.P. Rasmussen L.M. Williams Regulatory T cell lineage specification by the forkhead transcription factor foxp3 Immunity 22 3 2005 329 341
96. L.A. Dieleman B.U. Ridwan G.S. Tennyson Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice Gastroenterology 107 6 1994 1643 1652
97. J.L. Grogan R.M. Locksley T helper cell differentiation: on again, off again Curr Opin Immunol 14 3 2002 366 372
98. U.Y. Khoo I.E. Proctor A.J. Macpherson CD4+ T cell down-regulation in human intestinal mucosa: evidence for intestinal tolerance to luminal bacterial antigens J Immunol 158 8 1997 3626 3634
99. S.G. Johansson J.O. Hourihane J. Bousquet A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force Allergy 56 9 2001 813 824
100. S. Husby J.C. Jensenius S.E. Svehag Passage of undegraded dietary antigen into the blood of healthy adults. Further characterization of the kinetics of uptake and the size distribution of the antigen Scand J Immunol 24 4 1986 447 455
101. S. Husby J.C. Jensenius S.E. Svehag Passage of undegraded dietary antigen into the blood of healthy adults. Quantification, estimation of size distribution, and relation of uptake to levels of specific antibodies Scand J Immunol 22 1 1985 83 92
102. A.J. Macpherson T. Uhr Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria Science 303 5664 2004 1662 1665
103. H.A. Sampson Update on food allergy J Allergy Clin Immunol 113 5 2004 805 819 Quiz: 820
104. S.H. Sicherer D.Y. Leung Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects J Allergy Clin Immunol 118 1 2006 170 177
105. H. Breiteneder C. Ebner Molecular and biochemical classification of plant-derived food allergens J Allergy Clin Immunol 106 1 Pt 1 2000 27 36
106. M. Egger S. Mutschlechner N. Wopfner Pollen-food syndromes associated with weed pollinosis: an update from the molecular point of view Allergy 61 4 2006 461 476
107. H.A. Sampson Food allergy. Part 1: immunopathogenesis and clinical disorders J Allergy Clin Immunol 103 5 Pt 1 1999 717 728
108. D. Dombrowicz M. Capron Eosinophils, allergy and parasites Curr Opin Immunol 13 6 2001 716 720
109. S.P. Hogan A. Mishra E.B. Brandt A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy Proc Natl Acad Sci USA 97 12 2000 6681 6686
110. C. Gordon D. Wofsy Effects of recombinant murine tumor necrosis factor-alpha on immune function J Immunol 144 5 1990 1753 1758
111. M.N. Kweon M. Yamamoto M. Kajiki Systemically derived large intestinal CD4(+) Th2 cells play a central role in STAT6-mediated allergic diarrhea J Clin Invest 106 2 2000 199 206
112. K.L. Madsen J.S. Doyle M.M. Tavernini Antibiotic therapy attenuates colitis in interleukin 10 gene-deficient mice Gastroenterology 118 6 2000 1094 1105
113. R. Kühn J. Lohler D. Rennick Interleukin-10-deficient mice develop chronic enterocolitis Cell 75 1993 263 274
114. K.B. Hahm Y.H. Im T.W. Parks Loss of transforming growth factor beta signalling in the intestine contributes to tissue injury in inflammatory bowel disease Gut 49 2 2001 190 198
115. M.M. Shull I. Ormsby A.B. Kier Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease Nature 359 6397 1992 693 699
116. C.O. Elson R.B. Sartor G.S. Tennyson Experimental models of inflammatory bowel disease Gastroenterology 109 4 1995 1344 1367
117. R.S. Blumberg L.J. Saubermann W. Strober Animal models of mucosal inflammation and their relation to human inflammatory bowel disease Curr Opin Immunol 11 6 1999 648 656 (published erratum appears in Curr Opin Immunol 2000; 12(2): 226)
118. A.K. Bhan E. Mizoguchi R.N. Smith Colitis in transgenic and knockout animals as models of human inflammatory bowel disease Immunol Rev 169 1999 195 207
119. G. Bouma W. Strober The immunological and genetic basis of inflammatory bowel disease Nat Rev Immunol 3 2003 521
120. A. Mizoguchi E. Mizoguchi A.K. Bhan Immune networks in animal models of inflammatory bowel disease Inflamm Bowel Dis 9 4 2003 246 259
121. J.P. Hugot M. Chamaillard H. Zouali Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease Nature 411 6837 2001 599 603
122. Y. Ogura D.K. Bonen N. Inohara A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease Nature 411 6837 2001 603 606
123. J. Hampe A. Cuthbert P.J. Croucher Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations Lancet 357 9272 2001 1925 1928
124. P. Mombaerts E. Mizoguchi M.J. Grusby Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice Cell 75 1993 274 282
125. L. Qiao G. Schurmann M. Betzler Activation and signaling status of human lamina propria T lymphocytes Gastroenterology 101 6 1991 1529 1536
126. N. Corazza S. Eichenberger H.P. Eugster Nonlymphocyte-derived tumor necrosis factor is required for induction of colitis in recombination activating gene (RAG)2(−/−) mice upon transfer of CD4(+)CD45RB(hi) T cells J Exp Med 190 10 1999 1479 1492
127. M. Schenk A. Bouchon F. Seibold C. Mueller TREM-1-expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases J Clin Invest 117 2007 3097 4106