摘要：SummaryUpregulation and stabilization of Foxp3 expression in Tregs are essential for regulating Treg function and immune homeostasis. In this study, gp96 immunization showed obvious therapeutic effects in aLyn–/–mouse model of systemic lupus erythematosus. Moreover, gp96 alleviated the initiation and progression of MOG-induced experimental autoimmune encephalomyelitis. Immunization of gp96 increased Treg frequency, expansion, and suppressive function. Gene expression profiling identified the NF-κB family member p65 and c-Rel as the key transcription factors for enhanced Foxp3 expression in Treg by gp96. Mutant gp96 within its Toll-like receptor (TLR) binding domain, TLR2 knockout mice, and mice with cell-specific deletion of MyD88, were used to demonstrate that gp96 activated Tregs and induced Foxp3 expression via a TLR2-MyD88-mediated NF-κB signaling pathway. Taken together, these results show that gp96 immunization restricted antibody-induced and Th-induced autoimmune diseases by integrating Treg expansion and activation, indicating its potential clinical usefulness against autoimmune diseases.Graphical abstractDisplay OmittedHighlights•SLE symptoms inLyn–/–mice are ameliorated by gp96 immunization•Tregs expanded by gp96 provide potential in suppressing Th-mediated EAE•Gp96 promotes Treg proliferation, stability, and suppressive function•Gp96 binds to and activates Treg in a TLR2-MyD88-NF-кB-Foxp3 pathwayImmune response, Genomics, Molecular biology
