Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases

Summary: 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 initiatio...

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Autores principales:	Yuxiu Xu, Erlong Liu, Xialin Xie, Jiuru Wang, Huaguo Zheng, Ying Ju, Lizhao Chen, Changfei Li, Xuyu Zhou, Zihai Li, Xin Li, Songdong Meng
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Immune response, Genomics, Molecular biology Science Q
Acceso en línea:	https://doaj.org/article/2255ee2f5d894a2ba1e046fa83a0f70a
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spelling	oai:doaj.org-article:2255ee2f5d894a2ba1e046fa83a0f70a2021-11-28T04:36:32ZInduction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases2589-004210.1016/j.isci.2021.103445https://doaj.org/article/2255ee2f5d894a2ba1e046fa83a0f70a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221014164https://doaj.org/toc/2589-0042Summary: 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-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.Yuxiu XuErlong LiuXialin XieJiuru WangHuaguo ZhengYing JuLizhao ChenChangfei LiXuyu ZhouZihai LiXin LiSongdong MengElsevierarticleImmune response, Genomics, Molecular biologyScienceQENiScience, Vol 24, Iss 12, Pp 103445- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immune response, Genomics, Molecular biology Science Q
spellingShingle	Immune response, Genomics, Molecular biology Science Q Yuxiu Xu Erlong Liu Xialin Xie Jiuru Wang Huaguo Zheng Ying Ju Lizhao Chen Changfei Li Xuyu Zhou Zihai Li Xin Li Songdong Meng Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases
description	Summary: 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-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.
format	article
author	Yuxiu Xu Erlong Liu Xialin Xie Jiuru Wang Huaguo Zheng Ying Ju Lizhao Chen Changfei Li Xuyu Zhou Zihai Li Xin Li Songdong Meng
author_facet	Yuxiu Xu Erlong Liu Xialin Xie Jiuru Wang Huaguo Zheng Ying Ju Lizhao Chen Changfei Li Xuyu Zhou Zihai Li Xin Li Songdong Meng
author_sort	Yuxiu Xu
title	Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases
title_short	Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases
title_full	Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases
title_fullStr	Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases
title_full_unstemmed	Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases
title_sort	induction of foxp3 and activation of tregs by hsp gp96 for treatment of autoimmune diseases
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/2255ee2f5d894a2ba1e046fa83a0f70a
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Induction of Foxp3 and activation of Tregs by HSP gp96 for treatment of autoimmune diseases

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