CD24 aggravates acute liver injury in autoimmune hepatitis by promoting IFN-γ production by CD4(+) T cells.
CD24 aggravates acute liver injury in autoimmune hepatitis by promoting IFN-γ production by CD4(+) T cells.
复制标题
DOI：
10.1038/cmi.2016.57
复制
发表时间：
2018-03
影响因子：
24.1
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Zheng C;Yin S;Yang Y;Yu Y;Xie X
t细胞介导的免疫应答涉及许多临床肝损伤，如自身免疫性肝炎和急性病毒性肝炎。CD24在不同的免疫细胞中广泛表达，在许多自身免疫性疾病的发病机制中起重要作用。然而，CD24在t细胞介导的肝损伤中的作用至今尚未被阐明。在这里，我们发现CD24缺乏通过降低血清干扰素-γ (IFN-γ)水平来保护小鼠免受ConA诱导的暴发性肝损伤。ConA刺激后，肝T细胞CD24表达显著升高。此外，在cd24缺陷小鼠中检测到肝脏CD4+ T细胞产生IFN-γ减少，这与肝组织中STAT1磷酸化下调有关。体外实验也支持这样的结论：CD24缺乏会影响ConA、CD3/CD28和肉豆蔻酸酯/离子霉素刺激后CD4+ T细胞产生IFN-γ。我们的研究表明，CD24缺乏通过降低体内CD4+ t细胞依赖性IFN-γ的产生而具有肝保护作用，这表明CD24可能是减少临床肝炎的潜在靶分子。
The T-cell-mediated immune response is implicated in many clinical hepatic injuries, such as autoimmune hepatitis and acute virus hepatitis. CD24 is widely expressed by different immune cells and plays an important role in the pathogenesis of many autoimmune diseases. However, the role of CD24 in T-cell-mediated liver injury has not been elucidated until now. Here we showed that CD24 deficiency protects mice from concanavalin A (ConA)-induced fulminant liver injury by reducing serum interferon-γ (IFN-γ) levels. CD24 expression by hepatic T cells was markedly increased following ConA challenge. Moreover, decreased IFN-γ production by hepatic CD4+ T cells in CD24-deficient mice was detected, which was correlated with downregulated phosphorylation of STAT1 in hepatic tissue. In vitro experiments also supported the conclusion that CD24 deficiency impaired IFN-γ production by CD4+ T cells following ConA, CD3/CD28 and phorbol myristate acetate/ionomycin stimulation. Our study suggests that CD24 deficiency confers hepatoprotection by decreasing CD4+ T-cell-dependent IFN-γ production in vivo, which suggests that CD24 might be a potential target molecule for reducing clinical hepatitis.
登录
查看更多内容
影响因子：
15.3
作者：
Kaneko, Y;Harada, M;Kawano, T;Yamashita, M;Shibata, Y;Gejyo, F;Nakayama, T;Taniguchi, M
通讯作者：
Taniguchi, M
影响因子：
6.4
作者：
Chen, Yonglin;Peng, Hui;Tian, Zhigang
通讯作者：
Tian, Zhigang
影响因子：
3.1
作者：
Chen, Meng;Zhang, Lei;Li, Shufeng
通讯作者：
Li, Shufeng
影响因子：
32.4
作者：
Grivennikov, SI;Tumanov, AV;Nedospasov, SA
通讯作者：
Nedospasov, SA
影响因子：
4.4
作者：
Berga-Bolanos, Rosa;Drews-Elger, Katherine;Lopez-Rodriguez, Cristina
通讯作者：
Lopez-Rodriguez, Cristina