title: Interleukin-33 ameliorates experimental colitis through promoting Th2/Foxp3⁺ regulatory T-cell responses in mice.
abstract: Crohn's disease (CD) is characterized by the activation of Th1 and Th17 cells and deficiency of regulatory T cells (Tregs), leading to intestine tissue injury and destruction. As a novel cytokine of the interleukin (IL)-1 family, the role and underlying mechanisms of IL-33 in CD remain poorly understood. Here, we assess the effects and mechanisms of IL-33 on the trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis that mimics human CD. We found that IL-33 levels were increased in the TNBS-treated mice, whereas recombinant IL-33 (rIL-33) administration substantially ameliorated TNBS-mediated colonic tissue injury and clinical symptoms of colitis. The protective effect of rIL-33 was partly associated with the markedly increased induction of Th2-type cytokines. Importantly, rIL-33 treatment resulted in prominently upregulated Foxp3 expression in the TNBS-treated mice, and depletion of Tregs significantly abrogated the impact of IL-33 on reducing the development of colitis. Notably, the level of CD103⁺ dendritic cells (DCs), which promotes development of Tregs, is also increased in mesenteric lymph node and lamina propria of rIL-33-treated mice. The impact of rIL-33 on CD103⁺ DC induction was the result of indirectly upregulating intestine epithelial cells that produce thymic stromal lymphopoietin and retinoic acid but do not directly act on DCs. In conclusion, our data provide clear evidence that IL-33 plays a protective role in TNBS-induced colitis, which is closely related to a Th1-to-Th2/Treg switch. Thus, IL-33 is a promising candidate for the development of new treatments for CD.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Duan
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Ali
authors.initials: A
authors.lastname: Xiong
authors.forename: Quansong
authors.initials: Q
authors.lastname: Xia
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
authors.forename: Min
authors.initials: M
authors.lastname: Fang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D005786:Gene Expression Regulation; D007108:Immune Tolerance / Q000187:drug effects; D039001:Integrin alpha Chains / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C506535:Il33 protein, mouse; D039001:Integrin alpha Chains; D000067596:Interleukin-33; D007378:Interleukins; C091367:alpha E integrins