STING Drives CD4+T Cell Differentiation via JAK-STAT Signaling in Bullous Pemphigoid

Bullous pemphigoid (BP) is an autoimmune blistering disease with an increasing incidence in recent years; however, the underlying immune regulatory mechanisms remain largely unclear. As a critical signaling hub linking innate and adaptive immunity, stimulator of interferon genes (STING) has recently been implicated in the pathogenesis of various autoimmune diseases and may regulate tissue inflammation and immune homeostasis through modulation of CD4+ T cell responses. In this study, transcriptomic analysis revealed that differentially expressed genes in peripheral blood CD4+ T cells from BP patients were primarily enriched in the JAK-STAT signaling pathway, T cell activation and differentiation, and type I interferon (IFN-I)-related pathways. Pharmacological inhibition of STING markedly attenuated the aberrant activation of these signaling pathways. Our findings suggest that STING may contribute to BP immunopathogenesis by regulating the JAK-STAT signaling axis and promoting abnormal CD4+ T cell activation and differentiation, providing new insights into the molecular mechanisms underlying BP and identifying potential therapeutic targets.