DRP1 downregulation impairs mitophagy, driving mitochondrial ROS and SASP production in rheumatoid arthritis CD4PD-1T cells. (2025)

T cell senescence occurs in patients with rheumatoid arthritis (RA), but the specific phenotype and its contribution to tissue-destructive inflammation remain unclear. Here, we aim to investigate whether PD-1 marks pathogenic senescent CD4T cells and to explore the role and mechanism of senescent CD4PD-1T cells in RA pathogenesis. Here, we identified an expanded population of CD4PD-1T cells in RA patients that exhibited hallmark senescence features, including elevated senescence-associated secretory phenotype (SASP) production. Adoptive transfer experiments demonstrated that CD4PD-1T cells significantly accelerated disease progression in collagen-induced arthritis (CIA) models. Mechanistically, we demonstrated that RA CD4PD-1T cells showed decreased expression of dynamin-related protein 1