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.

journal_name

Immunology

journal_title

Immunology

authors

Chen Y,Peng H,Chen Y,Wei H,Sun R,Tian Z

doi

10.1111/imm.12201

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

388-400

issue

3

eissn

0019-2805

issn

1365-2567

journal_volume

141

pub_type

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