文章基本信息

标题：Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases
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作者：Yuxiu Xu ; Erlong Liu ; Xialin Xie 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：12
页码：1-25
DOI：10.1016/j.isci.2021.103445
语种：English
出版社：Elsevier
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