Rheumatoid Arthritis (RA) represents a chronic T cell-mediated inflammatory autoimmune disease. Studies have shown that epigenetic mechanisms contribute to the pathogenesis of RA. Histone deacetylases (HDACs) represent one important group of epigenetic regulators. However, the role of individual HDAC members for the pathogenesis of arthritis is still unknown. In this study we demonstrate that mice with a T cell-specific deletion of HDAC1 (HDAC1-cKO) are resistant to the development of Collagen-induced arthritis (CIA), whereas the antibody response to collagen type II was undisturbed, indicating an unaltered T cell-mediated B cell activation. The inflammatory cytokines IL-17 and IL-6 were significantly decreased in sera of HDAC1-cKO mice. IL-6 treated HDAC1-deficient CD4⁺ T cells showed an impaired upregulation of CCR6. Selective inhibition of class I HDACs with the HDAC inhibitor MS-275 under Th17-skewing conditions inhibited the upregulation of chemokine receptor 6 (CCR6) in mouse and human CD4⁺ T cells. Accordingly, analysis of human RNA-sequencing (RNA-seq) data and histological analysis of synovial tissue samples from human RA patients revealed the existence of CD4⁺CCR6⁺ cells with enhanced HDAC1 expression. Our data indicate a key role for HDAC1 for the pathogenesis of CIA and suggest that HDAC1 and other class I HDACs might be promising targets of selective HDAC inhibitors (HDACi) for the treatment of RA.

类风湿关节炎（RA）代表一种慢性T细胞介导的炎性自身免疫性疾病。研究表明表观遗传机制促进了RA的发病。组蛋白脱乙酰基酶（HDAC）代表了一组重要的表观遗传调节剂。但是，单个HDAC成员在关节炎的发病机制中的作用仍是未知的。在这项研究中，我们证明具有T细胞特异性HDAC1（HDAC1-cKO）缺失的小鼠对胶原诱导的关节炎（CIA）的发展具有抵抗力，而对II型胶原的抗体反应不受干扰，表明T不变细胞介导的B细胞活化。HDAC1-cKO小鼠的血清中炎性细胞因子IL-17和IL-6明显降低。IL-6治疗的HDAC1缺陷型CD4 ⁺T细胞显示出CCR6的上调受损。在Th17偏斜条件下，用HDAC抑制剂MS-275对I类HDAC的选择性抑制可抑制小鼠和人CD4 ⁺ T细胞中趋化因子受体6（CCR6）的上调。因此，对人类RNA测序（RNA-seq）数据的分析以及对来自人类RA患者的滑膜组织样品的组织学分析显示，存在HDAC1表达增强的CD4 ⁺ CCR6 ⁺细胞。我们的数据表明HDAC1在CIA的发病机理中起着关键作用，并暗示HDAC1和其他I类HDAC可能是用于治疗RA的选择性HDAC抑制剂（HDACi）的有希望的靶标。