title: CD49a promotes T-cell-mediated hepatitis by driving T helper 1 cytokine and interleukin-17 production.
abstract: It is becoming increasingly clear that the T-cell-mediated immune response is important in many diseases. In this study, we used concanavalin A (Con A) -induced hepatitis to investigate the role of CD49a in the molecular and cellular mechanism of the T-cell-mediated immune response. We found that CD49a(-/-) mice had significantly reduced levels of serum alanine aminotransferase and were protected from Con A-induced hepatitis. CD49a deficiency led to decreased production of interferon-γ (IFN-γ) and interleukin-17A (IL-17A) after Con A injection. Furthermore, we found that hepatic CD4(+) T cells and invariant natural killer T cells up-regulated CD49a expression, along with enhanced activation after Con A injection, leading to production of inflammatory cytokines by these T cells. Blockade of CD49a in vivo ameliorated Con A-induced hepatitis with reduced production of IFN-γ and IL-17A. Hence, CD49a promoted Con A-induced hepatitis through enhancing inflammatory cytokine production (IFN-γ and IL-17A) by CD4(+) T and invariant natural killer T cells. The protective effect of CD49a blockade antibody suggested a new target therapeutic molecule for intervention of T-cell-mediated liver injury.
authors.affiliation: Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Chen
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D003208:Concanavalin A; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D039423:Integrin alpha1 / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015415:Biomarkers; C098680:Il17a protein, mouse; D018836:Inflammation Mediators; D039423:Integrin alpha1; D020381:Interleukin-17; D003208:Concanavalin A; D007371:Interferon-gamma; D000410:Alanine Transaminase
keywords: CD49a; T-cell-mediated hepatitis; interferon-γ; interleukin-17A