The OX40/OX40L Axis Regulates T Follicular Helper Cell Differentiation: Implications for Autoimmune Diseases

T Follicular helper (Tfh) cells, a unique subset of CD4⁺ T cells, play an essential role in B cell development and the formation of germinal centers (GCs). Tfh differentiation depends on various factors including cytokines, transcription factors and multiple costimulatory molecules. Given that OX40 signaling is critical for costimulating T cell activation and function, its roles in regulating Tfh cells have attracted widespread attention. Recent data have shown that OX40/OX40L signaling can not only promote Tfh cell differentiation and maintain cell survival, but also enhance the helper function of Tfh for B cells. Moreover, upregulated OX40 signaling is related to abnormal Tfh activity that causes autoimmune diseases. This review describes the roles of OX40/OX40L in Tfh biology, including the mechanisms by which OX40 signaling regulates Tfh cell differentiation and functions, and their close relationship with autoimmune diseases.

OX40; OX40L; Tfh cells; autoimmune diseases; differentiation.