BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by inflammation and immune-mediated damage across multiple organ systems. Some patients with SLE respond poorly to conventional therapies. The pathogenesis of SLE is closely associated with dysregulated immune responses mediated by T follicular helper (Tfh) cells. OBJECTIVE: To comprehensively review the pathogenic role of Tfh cells in SLE and summarize major therapeutic targets and representative drugs, thereby highlighting the current translational landscape of Tfh-directed strategies. METHODS: Relevant studies on Tfh cells in SLE were reviewed, with emphasis on pathogenic mechanisms and therapeutic strategies targeting surface molecules, cytokines, transcription factors, and epigenetic and metabolic pathways. RESULTS: Targeting Tfh cell-associated surface molecules, cytokines, and transcription factors has shown promising therapeutic potential. Moreover, strategies targeting epigenetic and metabolic pathways, together with innovative modalities such as bispecific antibodies and chimeric antigen receptor T (CAR-T) cell therapies, represent emerging avenues for Tfh-targeted intervention in SLE. CONCLUSION: Tfh cells play a central role in SLE pathogenesis and represent a promising therapeutic target. Tfh-directed strategies may support the development of precision medicine approaches based on immune profiling and combination-targeted therapies. These advances offer a theoretical foundation for overcoming current therapeutic limitations.
Yang et al. (Thu,) studied this question.