AdipoR1 promotes pathogenic Th17 differentiation by regulating mitochondrial function through FUNDC1.

Abstract

Adiponectin receptor 1 ( Adipor1) deficiency has been shown to inhibit Th17 cell differentiation and reduce joint inflammation and bone erosion in antigen-induced arthritis (AIA) mice. Additional emerging evidence indicates that Th17 cells may differentiate into pathogenic (pTh17) and non-pathogenic (npTh17) cells, with the pTh17 cells playing a crucial role in numerous autoimmune and inflammatory conditions. In the current study, we found that Adipor1 deficiency inhibited pTh17 differentiation in vitro and that the deletion of Adipor1 in pTh17 cells reduced the mitochondrial function. RNA-sequencing (RNA-seq) demonstrated a significant increase in the expression levels of Fundc1, a gene related to mitochondrial function, in Adipor1-deficient CD4 + T cells. Interference with the Fundc1 expression in Adipor1-deficient CD4 + T cells partially mitigated the effect of Adipor1 deficiency on mitochondrial function and pTh17 differentiation. In conclusion, the current study demonstrated a novel role of AdipoR1 in regulating mitochondrial function via FUNDC1 to promote pTh17 cell differentiation, providing some insights into potential therapeutic targets for autoimmune and inflammatory diseases.