Systemic lupus erythematosus (SLE) is an autoimmune disease leading to considerable morbidity worldwide, which can be developed from a breakdown in immunological tolerance, resulting in T cell hyperactivation. T cell hyperactivation has been implicated in the tissue damage associated with many diseases. Although many researchers have identified the involvement of T-cell receptor-associated signaling molecules in T-cell activation, the mechanisms underlying this process are yet to be elaborated. In the current study, we set out to reveal a novel transcriptional mechanism required for CD4 + T cell immunoactivity involved in SLE. First of all, miR-124 was experimentally determined to be under-expressed in peripheral blood samples of SLE patients relative to healthy individuals. We further isolated CD4 + T cells from the peripheral blood samples of SLE patients and healthy individuals, and found that miR-124 was poorly expressed in peripheral blood-derived CD4 + T cells of SLE patients. Subsequent experiments demonstrated that re-expression of miR-124 inhibited the immunoactivity of CD4 + T cells from SLE patients, which was achieved through the down-regulation of IRF1 since dual-luciferase reporter gene assay findings indicated that miR-124 could target IRF1. In addition, HDAC1 was found to be enriched at the miR-124 promoter resulting in inhibition of miR-124 expression, thereby promoting the immunoactivity of CD4 + T cells. In conclusion, we identify that as a stimulator of CD4 + T cell immunoactivity, HDAC1 may be implicated in the immunopathology of SLE. The study will open up new avenues to explore future immunotherapy strategies for SLE.

系统性红斑狼疮 (SLE) 是一种自身免疫性疾病，在全球范围内导致相当多的发病率，其原因可能是免疫耐受性破坏，导致 T 细胞过度活化。T 细胞过度活化与许多疾病相关的组织损伤有关。尽管许多研究人员已经确定了T细胞受体相关信号分子在T-细胞激活，这一过程的潜在机制尚待阐明。在目前的研究中，我们着手揭示与 SLE 相关的 CD4 + T 细胞免疫活性所需的新转录机制。首先，实验确定 miR-124 在 SLE 患者的外周血样本中相对于健康个体表达不足。我们进一步从 SLE 患者和健康个体的外周血样本中分离出 CD4 + T 细胞，发现 miR-124 在 SLE 患者外周血来源的 CD4 + T 细胞中表达较差。随后的实验表明 miR-124 的重新表达抑制了 SLE 患者 CD4+T 细胞的免疫活性，这是通过下调 IRF1 实现的，因为双荧光素酶报告基因检测结果表明 miR-124 可以靶向 IRF1。此外，发现 HDAC1 在 miR-124 启动子处富集，从而抑制 miR-124 的表达，从而促进 CD4 + T 细胞的免疫活性。总之，我们确定作为 CD4 + T 细胞免疫活性的刺激物，HDAC1 可能与 SLE 的免疫病理学有关。该研究将为探索 SLE 的未来免疫治疗策略开辟新的途径。