title: IL-17A signaling in colonic epithelial cells inhibits pro-inflammatory cytokine production by enhancing the activity of ERK and PI3K.
abstract: Our previous data suggested that IL-17A contributes to the inhibition of Th1 cell function in the gut. However, the underlying mechanisms remain unclear. Here we demonstrate that IL-17A signaling in colonic epithelial cells (CECs) increases TNF-α-induced PI3K-AKT and ERK phosphorylation and inhibits TNF-α induced expression of IL-12P35 and of a Th1 cell chemokine, CXCL11 at mRNA level. In a co-culture system using HT-29 cells and PBMCs, IL-17A inhibited TNF-α-induced IL-12P35 expression by HT-29 cells and led to decreased expression of IFN-γ and T-bet by PBMCs. Finally, adoptive transfer of CECs from mice with Crohn's Disease (CD) led to an enhanced Th1 cell response and exacerbated colitis in CD mouse recipients. The pathogenic effect of CECs derived from CD mice was reversed by co-administration of recombinant IL-17A. Our data demonstrate a new IL-17A-mediated regulatory mechanism in CD. A better understanding of this pathway might shed new light on the pathogenesis of CD.
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China ; Department of Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Respiratory Medicine, First Affiliated Hospital of the Chinese PLA General Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Medical Engineering, Military General Hospital of Beijing PLA, Beijing, China.
authors.forename: Yueling
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Respiratory Medicine, First Affiliated Hospital of the Chinese PLA General Hospital, Beijing, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lang
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D054371:Chemokine CXCL11 / Q000037:antagonists & inhibitors; D018920:Coculture Techniques; D003092:Colitis / Q000378:metabolism; D003106:Colon; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D053765:Interleukin-12 Subunit p35; D020381:Interleukin-17 / Q000502:physiology*; D008807:Mice, Inbred BALB C; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D018417:Th1 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000730:Androstadienes; D002070:Butadienes; D054371:Chemokine CXCL11; D016207:Cytokines; D053765:Interleukin-12 Subunit p35; D020381:Interleukin-17; D009570:Nitriles; C515963:Traf3ip2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000077191:Wortmannin