Bcl2 like protein-12 suppresses Foxp3⁺ regulatory T cells in patients with rheumatoid arthritis

Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). Bcl2 like protein 12 (Bcl2L12) has the ability of immune regulation. This study aims to investigate the role of Bcl2L12 in interfering with Foxp3⁺ regulatory T cell (Treg) development and function in RA patients. In this study, RA patients were recruited in RA clinic. The peripheral blood samples were collected from RA patients and healthy (HA) subjects. Treg status was analyzed by a variety of immune assessing approaches. We observed that the frequency of Tregs in RA patients was significantly lower than that in HA subjects. The expression of Bcl2L12 was detected in CD4⁺ T cells, which was markedly higher in the RA group than that in HA group. Naive CD4⁺ T cells from RA patients were refractory to develop as Tregs. Inhibition of Bcl2L12 in CD4⁺ T cells from RA patients promoted Treg generation. Tregs isolated from RA patients showed functional defects, which could be restored by knocking down of Bcl2L12. In conclusion, Bcl2L12 plays a role in suppressing Treg development and function in RA patients. Inhibition of Bcl2L12 may have therapeutic potential in the treatment of RA.