The balance of intestinal Foxp3⁺ regulatory T cells and Th17 cells and its biological significance

References

• Round JL, O'Connell RM, Mazmanian SK. Coordination of tolerogenic immune responses by the commensal microbiota. J Autoimmun 2010;34(3):J220-5
   PubMed Web of Science ®Google Scholar
• Kim CH. Host and microbial factors in regulation of T cells in the intestine. Front Immunol 2013;4:141
   Google Scholar
• Brown EM, Sadarangani M, Finlay BB. The role of the immune system in governing host-microbe interactions in the intestine. Nat Immunol 2013;14(7):660-7
   PubMed Web of Science ®Google Scholar
• Maynard CL, Elson CO, Hatton RD, Weaver CT. Reciprocal interactions of the intestinal microbiota and immune system. Nature 2012;489(7415):231-41
   PubMed Web of Science ®Google Scholar
• Getnet D, Grosso JF, Goldberg MV, et al. A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells. Mol Immunol 2010;47(7-8):1595-600
   PubMed Web of Science ®Google Scholar
• Cong YZ. Molecular Gastronomy: how to Make the Critical Intestinal Foxp3(+) Treg Cell. Gastroenterology 2011;141(5):1559-62
   Google Scholar
• Lathrop SK, Bloom SM, Rao SM, et al. Peripheral education of the immune system by colonic commensal microbiota. Nature 2011;478(7368):250-4
   PubMed Web of Science ®Google Scholar
• Cebula A, Seweryn M, Rempala GA, et al. Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota. Nature 2013;497(7448):258-62
   PubMed Web of Science ®Google Scholar
• Kim SV, Xiang WV, Kwak C, et al. GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science 2013;340(6139):1456-9
   PubMed Web of Science ®Google Scholar
• Codarri L, Gyulveszi G, Tosevski V, et al. ROR gamma t drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011;12(6):560-7
   PubMed Web of Science ®Google Scholar
• El-Behi M, Ciric B, Dai H, et al. The encephalitogenicity of T(H)17 cells is dependent on IL-1-and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011;12(6):568-75
   PubMed Web of Science ®Google Scholar
• McGeachy MJ. GM-CSF: the secret weapon in the T(H)17 arsenal. Nat Immunol 2011;12(6):521-2
   PubMed Web of Science ®Google Scholar
• Fife BT, Pauken KE, Eagar TN, et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol 2009;10(11):1185-92
   PubMed Web of Science ®Google Scholar
• Chang SH, Dong C. Signaling of interleukin-17 family cytokines in immunity and inflammation. Cell Signal 2011;23(7):1069-75
   PubMed Web of Science ®Google Scholar
• Pickert G, Neufert C, Leppkes M, et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 2009;206(7):1465-72
   PubMed Web of Science ®Google Scholar
• Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol 2009;27:485-517
   PubMed Web of Science ®Google Scholar
• Lazarevic V, Chen X, Shim JH, et al. T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding ROR gamma t. Nat Immunol 2011;12(1):96-124
   PubMed Web of Science ®Google Scholar
• Schraml BU, Hildner K, Ise W, et al. The AP-1 transcription factor Batf controls T(H)17 differentiation. Nature 2009;460(7253):405-9
   PubMed Web of Science ®Google Scholar
• Bauquet AT, Jin HL, Paterson AM, et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and T-H-17 cells. Nat Immunol 2009;10(2):167-75
   PubMed Web of Science ®Google Scholar
• Veldhoen M, Hirota K, Westendorf AM, et al. The aryl hydrocarbon receptor links T(H)17-cell-mediated autoimmunity to environmental toxins. Nature 2008;453(7191):106-9
   PubMed Web of Science ®Google Scholar
• Ghoreschi K, Laurence A, Yang XP, et al. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 2010;467(7318):967-71
   PubMed Web of Science ®Google Scholar
• McGeachy MJ, Bak-Jensen KS, Chen Y, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology. Nat Immunol 2007;8(12):1390-7
   PubMed Web of Science ®Google Scholar
• Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 2010;140(6):845-5824
   PubMed Web of Science ®Google Scholar
• Denning TL, Norris BA, Medina-Contreras O, et al. Functional Specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization. J Immunol 2011;187(2):733-47
   Google Scholar
• del Rio ML, Bernhardt G, Rodriguez-Barbosa JI, Forster R. Development and functional specialization of CD103+ dendritic cells. Immunol Rev 2010;234:268-81
   PubMed Web of Science ®Google Scholar
• Scott CL, Aumeunier AM, Mowat AM. Intestinal CD103+ dendritic cells: master regulators of tolerance? Trends Immunol 2011;32(9):412-19
   PubMed Web of Science ®Google Scholar
• Farache J, Zigmond E, Shakhar G, Jung S. Contributions of dendritic cells and macrophages to intestinal homeostasis and immune defense. Immunol Cell Biol 2013;91(3):232-9
   Google Scholar
• Pabst O, Bernhardt G. The puzzle of intestinal lamina propria dendritic cells and macrophages. Eur J Immunol 2010;40(8):2107-11
   Google Scholar
• Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 2007;204(8):1757-64
   PubMed Web of Science ®Google Scholar
• Hadis U, Wahl B, Schulz O, et al. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 2011;34(2):237-46
   PubMed Web of Science ®Google Scholar
• Kawabe T, Sun S, Fujita T, et al. Homeostatic proliferation of naive CD4+ T cells in mesenteric lymph nodes generates gut-tropic Th17 cells. J Immunol 2013;190(11):5788-9832
   Google Scholar
• Cerovic V, Houston SA, Scott CL, et al. Intestinal CD103(-) dendritic cells migrate in lymph and prime effector T cells. Mucosal Immunol 2013;6(1):104-13
   Google Scholar
• Persson EK, Uronen-Hansson H, Semmrich M, et al. IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation. Immunity 2013;38(5):958-69
   PubMedGoogle Scholar
• Chang J, Burkett PR, Borges CM, et al. MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling. Proc Natl Acad Sci USA 2013;110(6):2270-5
   Google Scholar
• Shaw MH, Kamada N, Kim YG, Nunez G. Microbiota-induced IL-1 beta, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine. J Exp Med 2012;209(2):251-8
   PubMed Web of Science ®Google Scholar
• Kinnebrew MA, Buffie CG, Diehl GE, et al. Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 2012;36(2):276-87
   PubMed Web of Science ®Google Scholar
• Artis D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol 2008;8(6):411-20
   PubMed Web of Science ®Google Scholar
• McDole JR, Wheeler LW, McDonald KG, et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 2012;483(7389):345-9
   PubMed Web of Science ®Google Scholar
• Bilsborough J, George TC, Norment A, Viney JL. Mucosal CD8alpha+ DC, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties. Immunology 2003;108(4):481-92
   PubMed Web of Science ®Google Scholar
• Iliev ID, Mileti E, Matteoli G, et al. Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning. Mucosal Immunol 2009;2(4):340-50
   PubMed Web of Science ®Google Scholar
• Collins CB, Aherne CM, Kominsky D, et al. Retinoic Acid Attenuates Ileitis by Restoring the Balance Between T-Helper 17 and T Regulatory Cells. Gastroenterology 2011;141(5):1821-31
   Google Scholar
• Obata Y, Takahashi D, Ebisawa M, et al. Epithelial cell-intrinsic Notch signaling plays an essential role in the maintenance of gut immune homeostasis. J Immunol 2012;188(5):2427-36
   PubMed Web of Science ®Google Scholar
• Hehemann JH, Kelly AG, Pudlo NA, et al. Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes. Proc Natl Acad Sci USA 2012;109(48):19786-91
   PubMed Web of Science ®Google Scholar
• Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 2010;330(6012):1768-73
   PubMed Web of Science ®Google Scholar
• Frank DN, Amand ALS, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 2007;104(34):13780-5
   PubMed Web of Science ®Google Scholar
• Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009;9(5):313-23
   PubMed Web of Science ®Google Scholar
• Ivanov II, Frutos RD, Manel N, et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 2008;4(4):337-49
   PubMed Web of Science ®Google Scholar
• Atarashi K, Tanoue T, Honda K. Induction of lamina propria Th17 cells by intestinal commensal bacteria. Vaccine 2010;28(50):8036-8
   Google Scholar
• Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 2010;107(27):12204-9
   PubMed Web of Science ®Google Scholar
• Ivanov II, Atarashi K, Manel N, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009;139(3):485-98
   PubMed Web of Science ®Google Scholar
• Round JL, Lee SM, Li J, et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 2011;332(6032):974-7
   PubMed Web of Science ®Google Scholar
• Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 2008;453(7195):620-5
   PubMed Web of Science ®Google Scholar
• D'Angelo M, Billings PC, Pacifici M, et al. Authentic matrix vesicles contain active metalloproteases (MMP). a role for matrix vesicle-associated MMP-13 in activation of transforming growth factor-beta. J Biol Chem 2001;276(14):11347-53
   PubMed Web of Science ®Google Scholar
• Atarashi K, Tanoue T, Shima T, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011;331(6015):337-41
   PubMed Web of Science ®Google Scholar
• Atarashi K, Tanoue T, Oshima K, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013;500(7461):232-6
   PubMed Web of Science ®Google Scholar
• Zhou L, Lopes JE, Chong MM, et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008;453(7192):236-40
   PubMed Web of Science ®Google Scholar
• Chen Z, Lin F, Gao Y, et al. FOXP3 and RORgammat: transcriptional regulation of Treg and Th17. Int Immunopharmacol 2011;11(5):536-42
   PubMed Web of Science ®Google Scholar
• Yang XO, Nurieva R, Martinez GJ, et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 2008;29(1):44-56
   PubMed Web of Science ®Google Scholar
• Kryczek I, Wu K, Zhao E, et al. IL-17+ regulatory T cells in the microenvironments of chronic inflammation and cancer. J Immunol 2011;186(7):4388-95
   PubMed Web of Science ®Google Scholar
• Zhu JF, Davidson TS, Wei G, et al. Down-regulation of Gfi-1 expression by TGF-beta is important for differentiation of Th17 and CD103(+) inducible regulatory T cells. J Exp Med 2009;206(2):329-41
   Google Scholar
• Das J, Ren GW, Zhang LY, et al. Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med 2009;206(11):2407-16
   PubMed Web of Science ®Google Scholar
• Nurieva R, Yang XXO, Martinez G, et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007;448(7152):480-3
   PubMed Web of Science ®Google Scholar
• Zhou L, Ivanov II, Spolski R, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 2007;8(9):967-74
   PubMed Web of Science ®Google Scholar
• Zheng Y, Danilenko DM, Valdez P, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007;445(7128):648-1
   PubMed Web of Science ®Google Scholar
• de Wit J, Souwer Y, van Beelen AJ, et al. CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation. Blood 2011;118(23):6107-14
   Google Scholar
• Malhotra N, Robertson E, Kang J. SMAD2 Is Essential for TGF beta-mediated Th17 Cell Generation. J Biol Chem 2010;285(38):29044-8
   PubMed Web of Science ®Google Scholar
• Lee Y, Awasthi A, Yosef N, et al. Induction and molecular signature of pathogenic TH17 cells. Nat Immunol 2012;13(10):991-9
   PubMed Web of Science ®Google Scholar
• Hall JA, Grainger JR, Spencer SP, Belkaid Y. The role of retinoic acid in tolerance and immunity. Immunity 2011;35(1):13-22
   PubMed Web of Science ®Google Scholar
• Maynard CL, Hatton RD, Helms WS, et al. Contrasting roles for all-trans retinoic acid in TGF-beta-mediated induction of Foxp3 and Il10 genes in developing regulatory T cells. J Exp Med 2009;206(2):343-57
   Google Scholar
• Xiao S, Jin H, Korn T, et al. Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J Immunol 2008;181(4):2277-84
   PubMed Web of Science ®Google Scholar
• Mucida D, Park Y, Kim G, et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007;317(5835):256-60
   PubMed Web of Science ®Google Scholar
• Chang J, Thangamani S, Kim MH, et al. Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation. Eur J Immunol 2013;43(4):967-78
   Google Scholar
• Uematsu S, Fujimoto K, Jang MH, et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol 2008;9(7):769-76
   PubMed Web of Science ®Google Scholar
• DePaolo RW, Abadie V, Tang F, et al. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 2011;471(7337):220-4
   PubMed Web of Science ®Google Scholar
• Hall JA, Cannons JL, Grainger JR, et al. Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity 2011;34(3):435-47
   PubMed Web of Science ®Google Scholar
• Wang C, Kang SG, HogenEsch H, et al. Retinoic acid determines the precise tissue tropism of inflammatory Th17 cells in the intestine. J Immunol 2010;184(10):5519-26
   Google Scholar
• Huber S, Gagliani N, Esplugues E, et al. Th17 cells express interleukin-10 receptor and are controlled by Foxp3(-) and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner. Immunity 2011;34(4):554-65
   PubMed Web of Science ®Google Scholar
• Chaudhry A, Samstein RM, Treuting P, et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity 2011;34(4):566-78
   PubMed Web of Science ®Google Scholar
• Liu B, Tonkonogy SL, Sartor RB. Antigen-presenting cell production of IL-10 inhibits T-helper 1 and 17 cell responses and suppresses colitis in mice. Gastroenterology 2011;141(2):653-62. 662 e651-654
   Google Scholar
• Denning TL, Wang YC, Patel SR, et al. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol 2007;8(10):1086-94
   PubMed Web of Science ®Google Scholar
• Izcue A, Coombes JL, Powrie F. Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol 2009;27:313-38
   PubMed Web of Science ®Google Scholar
• Chaudhry A, Rudra D, Treuting P, et al. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 2009;326(5955):986-91
   Web of Science ®Google Scholar
• Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 2011;474(7351):298-306
   PubMed Web of Science ®Google Scholar
• Nishida A, Lau CW, Zhang M, et al. The membrane-bound mucin Muc1 regulates T helper 17-cell responses and colitis in mice. Gastroenterology 2012;142(4):865-74. e862
   Google Scholar
• Mikami Y, Kanai T, Sujino T, et al. Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis. Eur J Immunol 2010;40(9):2409-22
   Google Scholar
• Lee YK, Turner H, Maynard CL, et al. Late developmental plasticity in the T helper 17 lineage. Immunity 2009;30(1):92-107
   PubMed Web of Science ®Google Scholar
• Kanai T, Mikami Y, Sujino T, et al. ROR gamma t-dependent IL-17A-producing cells in the pathogenesis of intestinal inflammation. Mucosal Immunol 2012;5(3):240-7
   Google Scholar
• Sujino T, Kanai T, Ono Y, et al. Regulatory T cells suppress development of colitis, blocking differentiation of T-helper 17 into alternative T-helper 1 cells. Gastroenterology 2011;141(3):1014-23
   Google Scholar
• Hill DA, Artis D. Intestinal bacteria and the regulation of immune cell homeostasis. Annu Rev Immunol 2010;28:623-67
   PubMed Web of Science ®Google Scholar
• Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007;448(7152):427-34
   PubMed Web of Science ®Google Scholar
• Hommes DW, Mikhajlova TL, Stoinov S, et al. Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut 2006;55(8):1131-7
   PubMed Web of Science ®Google Scholar
• Reinisch W, Hommes DW, Van Assche G, et al. A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease. Gut 2006;55(8):1138-44
   PubMed Web of Science ®Google Scholar
• Geremia A, Biancheri P, Allan P, et al. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 2014;13(1):3-10
   PubMed Web of Science ®Google Scholar
• Doherty GA, Bai AP, Hanidziar D, et al. CD73 is a phenotypic marker of effector memory Th17 cells in inflammatory bowel disease. Eur J Immunol 2012;42(11):3062-72
   Google Scholar
• Fujitake Y, Ohstuka Y, Ikuse T, et al. The analysis of inflammatory signals in Japanese children with Crohn's disease. Pediatr Int 2013;55(6):753-6
   Google Scholar
• Van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology 2008;135(4):1114-22
   PubMed Web of Science ®Google Scholar
• Spencer DM, Veldman GM, Banerjee S, et al. Distinct inflammatory mechanisms mediate early versus late colitis in mice. Gastroenterology 2002;122(1):94-105
   Google Scholar
• Fichtner-Feigl S, Fuss IJ, Young CA, et al. Induction of IL-13 triggers TGF-beta1-dependent tissue fibrosis in chronic 2,4,6-trinitrobenzene sulfonic acid colitis. J Immunol 2007;178(9):5859-70
   PubMed Web of Science ®Google Scholar
• Monteleone G, Caruso R, Pallone F. Targets for new immunomodulation strategies in inflammatory bowel disease. Autoimmun Rev 2014;13(1):11-14
   Google Scholar
• Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med 2012;367(7):616-24
   PubMed Web of Science ®Google Scholar
• Hovhannisyan Z, Treatman J, Littman DR, Mayer L. Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases. Gastroenterology 2011;140(3):957-65
   PubMed Web of Science ®Google Scholar
• Voo KS, Wang YH, Santori FR, et al. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci USA 2009;106(12):4793-8
   PubMed Web of Science ®Google Scholar
• Monteleone G, Boirivant M, Pallone F, MacDonald TT. TGF-beta1 and Smad7 in the regulation of IBD. Mucosal Immunol 2008;1(Suppl 1):S50-3
   Google Scholar
• Desreumaux P. Specific targeting of IL-6 signalling pathway: a new way to treat IBD? Gut 2000;47(4):465-6
   Google Scholar
• Bai A, Lu N, Guo Y, et al. All-trans retinoic acid down-regulates inflammatory responses by shifting the Treg/Th17 profile in human ulcerative and murine colitis. J Leukoc Biol 2009;86(4):959-69
   Google Scholar
• Dong Z, Du L, Xu X, et al. Aberrant expression of circulating Th17, Th1 and Tc1 cells in patients with active and inactive ulcerative colitis. Int J Mole Med 2013;31(4):989-97
   Google Scholar
• Kobayashi T, Okamoto S, Hisamatsu T, et al. IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease. Gut 2008;57(12):1682-9
   PubMed Web of Science ®Google Scholar
• Lazarev M, Huang CR, Bitton A, et al. Relationship between proximal Crohn's disease location and disease behavior and surgery: a cross-sectional study of the IBD Genetics Consortium. Am J Gastroenterol 2013;108(1):106-12
   PubMed Web of Science ®Google Scholar
• Gallimore AM, Godkin A. Epithelial barriers, microbiota, and colorectal cancer. N Engl J Med 2013;368(3):282-4
   PubMed Web of Science ®Google Scholar
• Hyun YS, Han DS, Lee AR, et al. Role of IL-17A in the development of colitis-associated cancer. Carcinogenesis 2012;33(4):931-6
   Google Scholar
• Stolfi C, Rizzo A, Franze E, et al. Involvement of interleukin-21 in the regulation of colitis-associated colon cancer. J Exp Med 2011;208(11):2279-90
   Google Scholar
• Jiang RQ, Wang HY, Deng L, et al. IL-22 is related to development of human colon cancer by activation of STAT3. BMC Cancer 2013;13:59
   PubMed Web of Science ®Google Scholar
• Tong Z, Yang XO, Yan H, et al. A protective role by interleukin-17F in colon tumorigenesis. PLoS One 2012;7(4):e34959
   Google Scholar
• Grivennikov SI, Wang K, Mucida D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012;491(7423):254-8
   PubMed Web of Science ®Google Scholar
• Wu S, Rhee KJ, Albesiano E, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 2009;15(9):1016-22
   PubMed Web of Science ®Google Scholar
• Tosolini M, Kirilovsky A, Mlecnik B, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 2011;71(4):1263-71
   PubMed Web of Science ®Google Scholar
• Ogawa A, Andoh A, Araki Y, et al. Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol 2004;110(1):55-62
   PubMed Web of Science ®Google Scholar
• Zhang Z, Zheng M, Bindas J, et al. Critical role of IL-17 receptor signaling in acute TNBS-induced colitis. Inflamm Bowel Dis 2006;12(5):382-8
   PubMed Web of Science ®Google Scholar
• Feng T, Qin HW, Wang LF, et al. Th17 Cells Induce Colitis and Promote Th1 Cell Responses through IL-17 Induction of Innate IL-12 and IL-23 Production. J Immunol 2011;186(11):6313-18
   PubMedGoogle Scholar
• Seiderer J, Elben I, Diegelmann J, et al. Role of the novel th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.Hisl6lArg polymorphism in IBD. Inflamm Bowel Dis 2008;14(4):437-45
   PubMed Web of Science ®Google Scholar
• Fantini MC, Rizzo A, Fina D, et al. IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells. Eur J Immunol 2007;37(11):3155-63
   Google Scholar
• Sugimoto K, Ogawa A, Mizoguchi E, et al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest 2008;118(2):534-44
   PubMed Web of Science ®Google Scholar
• Wiekowski MT, Leach MW, Evans EW, et al. Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J Immunol 2001;166(12):7563-70
   PubMed Web of Science ®Google Scholar
• Wang YQ, Ugai S, Shimozato O, et al. Induction of systemic immunity by expression of interleukin-23 in murine colon carcinoma cells. J Int Cancer 2003;105(6):820-4
   Google Scholar
• Becker C, Dornhoff H, Neufert C, et al. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J Immunol 2006;177(5):2760-4
   PubMed Web of Science ®Google Scholar
• Holtta V, Klemetti P, Sipponen T, et al. IL-23/IL-17 immunity as a hallmark of Crohn's disease. Inflamm Bowel Dis 2008;14(9):1175-84
   Web of Science ®Google Scholar
• Suzuki H, Ogawa H, Miura K, et al. IL-23 directly enhances the proliferative and invasive activities of colorectal carcinoma. Oncol Let 2012;4(2):199-204
   PubMed Web of Science ®Google Scholar