CD49a promotes T‐cell‐mediated hepatitis by driving T helper 1 cytokine and interleukin‐17 production. Issue 3 (March 2014)

• Record Type: Journal Article
• Authors: Chen, Yonglin; Peng, Hui; Chen, Yongyan; Wei, Haiming; Sun, Rui; Tian, Zhigang
• Is Part Of: Immunology. Volume 141:Issue 3(2014:Mar.)
• Page Start: 388
• Page End: 400
• Publication Date: 2014-03
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12201
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12201-abs-0001"> <title>Summary</title> <p>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‐<italic>γ</italic> (IFN‐<italic>γ</italic>) 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 <italic>in vivo</italic> ameliorated Con A‐induced hepatitis with reduced production of IFN‐<italic>γ</italic> and IL‐17A. Hence, CD49a promoted Con A‐induced hepatitis through enhancing inflammatory cytokine production (IFN‐<italic>γ</italic> 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.</p> </abstract>