Deficiency of Pink1 promotes the differentiation of Th1 cells

Abstract

Previous studies have found that Pink1 is crucial for T cell activation and the function of Treg cells. However, the effect of Pink1 on inflammatory Th1 cells is largely unknown. In the process of Th1 differentiation from human naïve T cells, we found a reduction of Pink1 and Parkin. We then focused our attention on the Pink1 KO mice. Although there was no difference in the baseline of the T cell subset of Pink1 KO mice, Th1 differentiation from Pink1 KO naïve T cells in vitro showed a significant increase. Subsequently, we transferred naïve CD4⁺ T cells into Rag2 KO mice to establish a T-cell colitis mouse model and found that CD4⁺ T cells in mesentery lymph nodes of mice receiving Pink1 KO cells increased significantly, especially Th1 cells. Intestinal IHC staining also showed that the transcription factor T-bet of Th1 increased. Treatment of CD4⁺ T cells from lupus-like mice with mitophagy agonist urolithin A, a reduction of Th1 cells was observed, suggesting the clinical value of using mitophagy agonists to suppress Th1-dominated disease in the future.

Keywords: MRL/lpr; Mitophagy; PINK1; T cell differentiation.