| First Author | Xu Y | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 12 | Pages | 103445 |
| PubMed ID | 34877502 | Mgi Jnum | J:321705 |
| Mgi Id | MGI:6835628 | Doi | 10.1016/j.isci.2021.103445 |
| Citation | Xu Y, et al. (2021) Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases. iScience 24(12):103445 |
| abstractText | Upregulation 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 a Lyn (-/-) 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-kappaB 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-kappaB 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. |
