Plasma extracellular vesicles promote follicular T helper cell expansion in primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is a prevalent autoimmune disease characterized by exocrine gland dysfunction, with hallmarks of B cell and T cell overactivation, whose underlying mechanism remains largely unknown. Herein, we show that pSS plasma contained more extracellular vesicles (EVs) than HC plasma, which promoted CD4⁺ T cell activation, Th1, and follicular T helper cell (Tfh) differentiation, aggravating pSS immunopathology. Notably, pSS plasma EVs were enriched with miR-501–3p, mediating CD4⁺ T cell activation and Tfh cell differentiation. Furthermore, miR-501–3p downregulated special AT-rich sequence-binding protein-1 (SATB1) to promote Tfh differentiation. These findings suggested pSS plasma EVs as an important contributor to pSS pathogenesis, which was of potential clinical interest in managing pSS.