GIT2 deficiency attenuates concanavalin A-induced hepatitis in mice

• Published in: FEBS open bio Vol. 5; no. 1; pp. 688 - 704
• Main Authors: Hao, Yu-E, He, Dong-Fang, Yin, Rong-Hua, Chen, Hui, Wang, Jian, Wang, Shao-Xia, Zhan, Yi-Qun, Ge, Chang-Hui, Li, Chang-Yan, Yu, Miao, Yang, Xiao-Ming
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.01.2015; John Wiley & Sons, Inc; Elsevier; Wiley
• Subjects: Binding sites; CD4 antigen; Cell activation; Cell division; Cell proliferation; Concanavalin A; Cytokines; Cytoskeleton; GIT2; Hepatitis; Immunology; Inflammation; Injuries; Innate immunity; Internalization; Kinases; Knock-out mice; Liver diseases; Lymphocytes; Lymphocytes T; Proteins; Research article; Signal transduction; Statistical analysis; T cell activation; T cell receptors; Thymocytes; Tumor necrosis factor-TNF; GFP; GIT2; Hepatitis; TCR; T cell activation; PMA; Knock-out mice; Con A; Innate immunity; FACS; GFP, green fluorescent protein; Con A, concanavalin A; FACS, fluorescence-activated cell sorting; GIT2, G protein-coupled receptor kinase interactor 2; PMA, 4b-phorbol 12-myristate 13-acetate; TCR, T cell receptor
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1016/j.fob.2015.08.005

•GIT2 depletion attenuates Con A-induced immunological hepatic injuries.•GIT2 depletion suppressed the activation and function of mouse CD4+ T cells.•GIT2 depletion suppressed liver infiltration by lymphoid cells after Con A treatment.•There were lower levels of proinflammatory cytokines in Git2−/− mice after Con A injection. G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs). The short-splice form of GIT2 is expressed in peripheral T cells and thymocytes. However, the functions of GIT2 in T cells have not yet been determined. We show that treatment with Con A in a model of polyclonal T-lymphocyte activation resulted in marked inhibitions in the intrahepatic infiltration of inflammatory cells, cytokine response and acute liver failure in Git2−/− mice. CD4+ T cells from Git2−/− mice showed significant impairment in proliferation, cytokine production and signal transduction upon TCR-stimulated activation. Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.