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

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.