title: Blockade of IL-33 ameliorates Con A-induced hepatic injury by reducing NKT cell activation and IFN-γ production in mice.
abstract: IL-33, a recently described member of the IL-1 family, has been identified as a cytokine endowed with pro-Th2 type functions. To date, there are only limited data on its role in physiological and pathological hepatic immune responses. In this study, we examined the role of IL-33 in immune-mediated liver injury by exploring the model of concanavalin A (Con A)-induced hepatitis. We observed that the level of IL-33 expression in the liver was dramatically increased at 12 h after Con A injection. Meanwhile, ST2L, the receptor of IL-33, was significantly up-regulated in lymphocytes including T and natural killer T (NKT) cells, especially in NKT cells. Moreover, administration of recombinant IL-33 exacerbated Con A-induced hepatitis, while pretreatment of IL-33-blocking antibody or psST2-Fc plasmids showed a protective effect probably by inhibiting the activation of late stage of T cells and NKT cells and also decreasing the production of the cytokine IFN-γ. Furthermore, depletion of NKT cells abolished the protective effect of IL-33-blocking antibody, and IL-33 failed to exacerbate Con A-induced hepatitis in IFN-γ(-/-) mice. These data suggested the critical roles of NKT cells and IFN-γ in the involvement of IL-33 in Con A-induced hepatitis. Blockade of IL-33 may represent a novel therapeutic strategy through IL-33/ST2L signal to prevent immune-mediated liver injury.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Rd. 13#, Wuhan 430030, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Lihua
authors.initials: L
authors.lastname: Duan
authors.forename: Ali
authors.initials: A
authors.lastname: Xiong
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
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; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000906:Antibodies; C506535:Il33 protein, mouse; D007375:Interleukin-1; D000067596:Interleukin-33; D007378:Interleukins; D003208:Concanavalin A; D007371:Interferon-gamma