AdipoR1 promotes pathogenic Th17 differentiation by regulating mitochondrial function through FUNDC1

Adiponectin receptor 1 ( <i>Adipor1</i>) deficiency has been shown to inhibit Th17 cell differentiation and reduce joint inflammation and bone erosion in antigen-induced arthritis 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 <i>Adipor1</i> deficiency inhibited pTh17 differentiation <i>in vitro</i> and induced mitochondrial dysfunction in pTh17 cells. RNA sequencing demonstrated a significant increase in the expression levels of <i>Fundc1</i>, a gene related to mitochondrial function, in <i>Adipor1</i>-deficient CD4 ⁺ T cells. <i>Fundc1</i> knockdown in <i>Adipor1</i>-deficient CD4 ⁺ T cells partially reversed the effects of <i>Adipor1</i> deficiency on mitochondrial function and pTh17 differentiation. In conclusion, the current study demonstrated a novel role of <i>Adipor1</i> in regulating mitochondrial function <i>via</i> <i>Fundc1</i> to promote pTh17 cell differentiation, providing some insight into potential therapeutic targets for autoimmune and inflammatory diseases.