HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies.
HDAC6 regulates IL-17 expression in T lymphocytes: implications for HDAC6-targeted therapies.
复制标题
HDAC6 调节 T 淋巴细胞中 IL-17 的表达：对 HDAC6 靶向治疗的影响
作者：
Yan B;Liu Y;Bai H;Chen M;Xie S;Li D;Liu M;Zhou J
促炎细胞因子白细胞介素17（IL-17）与免疫和炎症密切相关。辅助性T细胞17和γδ T细胞是免疫系统中IL-17的主要来源。然而，IL-17在T细胞中的表达调节机制仍然难以捉摸。在这里，我们证明了小鼠组蛋白脱乙酰酶6（HDAC 6）的缺失不会影响CD 4+或CD 8 + T细胞的产生，但会刺激产生IL-17的γδ T细胞的发育。我们的数据进一步表明HDAC 6缺乏增加了脾和淋巴结中Vγ4+ γδ T细胞的IL-17产生。与这些观察结果一致，γδ T细胞中HDAC 6活性的小分子抑制促进体外IL-17的表达。因此，这些数据揭示了HDAC 6抑制T细胞中IL-17的产生，为HDAC 6在免疫系统中的作用提供了新的见解。这些发现对HDAC 6靶向治疗的临床研究也具有重要意义。
The pro-inflammatory cytokine interleukin 17 (IL-17) is critically involved in immunity and inflammation. T-helper 17 and γδ T cells are the predominant sources of IL-17 in the immune system. However, the mechanisms by which the expression of IL-17 is regulated in T cells remain elusive. Here, we demonstrate that loss of histone deacetylase 6 (HDAC6) in mice does not affect the generation of CD4+ or CD8+ T cells, but stimulates the development of IL-17-producing γδ T cells. Our data further show that HDAC6 deficiency increases the production of IL-17 by Vγ4+ γδ T cells in the spleen and lymph nodes. Consistent with these observations, small-molecule inhibition of HDAC6 activity in γδ T cells promotes the expression of IL-17 in vitro. These data thus reveal that HDAC6 represses IL-17 production in T cells, providing novel insights into the role of HDAC6 in the immune system. These findings also have important implications for the clinical investigation of HDAC6-targeted therapies.