title: IL-21/IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice.
abstract: Serum level of IL-21 is increased in patients with inflammatory bowel diseases (IBD), suggesting that IL-21/IL-21 receptor (IL-21R) signaling may be involved in the pathogenesis of IBD. However, the role of IL-21/IL-21 receptor signaling plays in the pathogenesis of IBD is not very clear. In this study, using IL-21R.KO mice, we tested the role of IL-21/IL-21R signaling in the regulation of T helper cell responses during intestinal inflammation. Here we found that IL-21R.KO mice were more susceptible to DSS-induced colitis as compared with C57BL/6 mice. The spontaneous inflammatory cytokines released by macrophages in LP of colon were significantly increased, and Th2, Th17 and Treg responses were down-regulated markedly. However, Th1 responses were significantly up-regulated in IL-21R.KO mice. Meanwhile, the population of CD8(+)CD44(+)IFN-γ(+) T cells was markedly elevated in LP of inflammatory intestine of IL-21RKO mice. In vivo, after disease onset, DSS-induced intestinal inflammation was ameliorated in C57BL/6 mice treated with rIL-21. Our results demonstrate that IL-21/IL-21R signaling contributes to protection against DSS-induced acute colitis through suppression of Th1 and activation of Th2, Th17 and Treg responses in mice. Therefore, therapeutic manipulation of IL-21/IL-21R activity may allow improved immunotherapy for IBD and other inflammatory diseases associated with Th cell responses.
authors.affiliation: Department of anesthesiology, The Fourth Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Life Science School, Liaoning University, Shenyang, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.|Laboratory Medicine Department, Sheng Jing Hospital of China Medical University, Shenyang, China.
authors.lastname: Dan Yue
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University, Shenyang, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Northeast Pharmaceutical Group Co., Ltd, Shenyang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Changlong
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Division of Host Defense, Center for Prevention of Infectious Disease, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D053738:Interleukin-21 Receptor alpha Subunit / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D016264:Dextran Sulfate; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D000097043:Interleukin-22; C508118:Il21r protein, mouse