CD49a promotes T-cell-mediated hepatitis by driving T helper 1 cytokine and interleukin-17 production
CD49a promotes T-cell-mediated hepatitis by driving T helper 1 cytokine and interleukin-17 production
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DOI：
10.1111/imm.12201
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发表时间：
2014-03-01
期刊：
影响因子：
6.4
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
Chen, Yonglin;Peng, Hui;Tian, Zhigang
越来越清楚的是，T细胞介导的免疫应答在许多疾病中是重要的。在这项研究中，我们使用刀豆球蛋白A（ConA）诱导的肝炎，研究CD 49 a在T细胞介导的免疫反应的分子和细胞机制中的作用。我们发现，CD 49 a（-/-）小鼠血清丙氨酸氨基转移酶水平显着降低，并保护ConA诱导的肝炎。CD 49 a缺陷导致ConA注射后干扰素（IFN-）和白细胞介素-17A（IL-17 A）的产生减少。此外，我们还发现，肝脏CD 4（+）T细胞和恒定的自然杀伤T细胞上调CD 49 a的表达，沿着ConA注射后增强的活化，导致这些T细胞产生炎性细胞因子。体内阻断CD 49 a可改善ConA诱导的肝炎，减少IFN-γ和IL-17 A的产生。因此，CD 49 a通过增强CD 4（+）T细胞和恒定自然杀伤T细胞产生的炎性细胞因子（IFN-和IL-17 A）来促进ConA诱导的肝炎。CD 49 a阻断抗体的保护作用为T细胞介导的肝损伤的干预提供了新的靶向治疗分子。
It is becoming increasingly clear that the T-cell-mediated immune response is important in many diseases. In this study, we used concanavalin A (ConA) -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 ConA-induced hepatitis. CD49a deficiency led to decreased production of interferon- (IFN-) and interleukin-17A (IL-17A) after ConA injection. Furthermore, we found that hepatic CD4(+) T cells and invariant natural killer T cells up-regulated CD49a expression, along with enhanced activation after ConA injection, leading to production of inflammatory cytokines by these T cells. Blockade of CD49a in vivo ameliorated ConA-induced hepatitis with reduced production of IFN- and IL-17A. Hence, CD49a promoted ConA-induced hepatitis through enhancing inflammatory cytokine production (IFN- 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.