HDAC1 potentiates CD4 + T cell activation by inhibiting miR-124 and promoting IRF1 in systemic lupus erythematosus

• Published in: Cellular immunology 2021-04, Vol.362, p.104284-104284, Article 104284
• Main Authors: Chen, Jie, Peng, Lihui, Zhao, Zixia, Yang, Qiuyu, Yin, Feng, Liu, Mao, Luo, Xiao, He, Chengsong, He, Yue
• Format: Article
• Language: English
• Subjects: CD4+ T cells; HDAC1; Immunoactivity; IRF1; miR-124; Systemic lupus erythematosus
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2021.104284

•miR-124 is downregulated in peripheral blood and CD4 + T cell from SLE patients.•miR-124 targets and negatively regulates IRF1 expression in SLE.•HDAC1 binds to miR-124 promoter to inhibit miR-124 via deacetylation.•HDAC1 enhances CD4 + T cell immunoactivity by regulating miR-124 and IRF1.•This study lays a theoretical foundation for finding new target for SLE. 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.