HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1

Background: Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder and the decreased number and immunosuppressive dysfunction of Treg cells are key promoters of ITP. However, their mechanisms in ITP development have not been fully clarified.Methods: HUWE1 mRNA and protein levels in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jianqin Li, Yalin Xia, Xiaoru Fan, Xiaofang Wu, Feiyun Yang, Shaoyan Hu, Zhaoyue Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	HUWE1 ETS-1 treg cells immune thrombocytopenic purpura CD4+ Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/98fc416cd40c488cbf3af8af16defbf9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:98fc416cd40c488cbf3af8af16defbf9
record_format	dspace
spelling	oai:doaj.org-article:98fc416cd40c488cbf3af8af16defbf92021-12-01T02:34:30ZHUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-12296-634X10.3389/fcell.2021.708562https://doaj.org/article/98fc416cd40c488cbf3af8af16defbf92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.708562/fullhttps://doaj.org/toc/2296-634XBackground: Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder and the decreased number and immunosuppressive dysfunction of Treg cells are key promoters of ITP. However, their mechanisms in ITP development have not been fully clarified.Methods: HUWE1 mRNA and protein levels in CD4+ T cells in peripheral blood from ITP patients were assessed by quantitative real-time PCR and Western blot. HUWE1 function in ITP was estimated using flow cytometry, enzyme-linked immunosorbent assay and immunosuppression assay. Besides, the HUWE1 mechanism in reducing the number and function of Treg cells in ITP was investigated by immunoprecipitation, cycloheximide-chase assay, ubiquitin experiment and immunofluorescence assay.Results: HUWE1 expression was elevated in CD4+ T cells in peripheral blood from ITP patients and HUWE1 mRNA level was negatively correlated with platelet counts and Treg cell percentage. Moreover, the interference with HUWE1 increased the number of Treg cells and enhanced its immunosuppressive function, and the HUWE1 overexpression produced the opposite results. For the exploration of mechanism, HUWE1 interacted with E26 transformation-specific-1 (Ets-1) and this binding was dependent on the negative regulation of the phosphorylation level of Ets-1 (Thr38) and HUWE1 facilitated the ubiquitin degradation of Ets-1 protein to restrain Treg cell differentiation and weaken their immunosuppressive functions. The in vivo assay confirmed that the HUWE1 inhibitor alleviated ITP in mice.Conclusion: HUWE1 induced the immune imbalance in ITP by decreasing the number and weakening the function of Treg cells through the ubiquitination degradation of Ets-1.Jianqin LiYalin XiaXiaoru FanXiaofang WuFeiyun YangShaoyan HuZhaoyue WangFrontiers Media S.A.articleHUWE1ETS-1treg cellsimmune thrombocytopenic purpuraCD4+Biology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HUWE1 ETS-1 treg cells immune thrombocytopenic purpura CD4+ Biology (General) QH301-705.5
spellingShingle	HUWE1 ETS-1 treg cells immune thrombocytopenic purpura CD4+ Biology (General) QH301-705.5 Jianqin Li Yalin Xia Xiaoru Fan Xiaofang Wu Feiyun Yang Shaoyan Hu Zhaoyue Wang HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1
description	Background: Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder and the decreased number and immunosuppressive dysfunction of Treg cells are key promoters of ITP. However, their mechanisms in ITP development have not been fully clarified.Methods: HUWE1 mRNA and protein levels in CD4+ T cells in peripheral blood from ITP patients were assessed by quantitative real-time PCR and Western blot. HUWE1 function in ITP was estimated using flow cytometry, enzyme-linked immunosorbent assay and immunosuppression assay. Besides, the HUWE1 mechanism in reducing the number and function of Treg cells in ITP was investigated by immunoprecipitation, cycloheximide-chase assay, ubiquitin experiment and immunofluorescence assay.Results: HUWE1 expression was elevated in CD4+ T cells in peripheral blood from ITP patients and HUWE1 mRNA level was negatively correlated with platelet counts and Treg cell percentage. Moreover, the interference with HUWE1 increased the number of Treg cells and enhanced its immunosuppressive function, and the HUWE1 overexpression produced the opposite results. For the exploration of mechanism, HUWE1 interacted with E26 transformation-specific-1 (Ets-1) and this binding was dependent on the negative regulation of the phosphorylation level of Ets-1 (Thr38) and HUWE1 facilitated the ubiquitin degradation of Ets-1 protein to restrain Treg cell differentiation and weaken their immunosuppressive functions. The in vivo assay confirmed that the HUWE1 inhibitor alleviated ITP in mice.Conclusion: HUWE1 induced the immune imbalance in ITP by decreasing the number and weakening the function of Treg cells through the ubiquitination degradation of Ets-1.
format	article
author	Jianqin Li Yalin Xia Xiaoru Fan Xiaofang Wu Feiyun Yang Shaoyan Hu Zhaoyue Wang
author_facet	Jianqin Li Yalin Xia Xiaoru Fan Xiaofang Wu Feiyun Yang Shaoyan Hu Zhaoyue Wang
author_sort	Jianqin Li
title	HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1
title_short	HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1
title_full	HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1
title_fullStr	HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1
title_full_unstemmed	HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1
title_sort	huwe1 causes an immune imbalance in immune thrombocytopenic purpura by reducing the number and function of treg cells through the ubiquitination degradation of ets-1
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/98fc416cd40c488cbf3af8af16defbf9
work_keys_str_mv	AT jianqinli huwe1causesanimmuneimbalanceinimmunethrombocytopenicpurpurabyreducingthenumberandfunctionoftregcellsthroughtheubiquitinationdegradationofets1 AT yalinxia huwe1causesanimmuneimbalanceinimmunethrombocytopenicpurpurabyreducingthenumberandfunctionoftregcellsthroughtheubiquitinationdegradationofets1 AT xiaorufan huwe1causesanimmuneimbalanceinimmunethrombocytopenicpurpurabyreducingthenumberandfunctionoftregcellsthroughtheubiquitinationdegradationofets1 AT xiaofangwu huwe1causesanimmuneimbalanceinimmunethrombocytopenicpurpurabyreducingthenumberandfunctionoftregcellsthroughtheubiquitinationdegradationofets1 AT feiyunyang huwe1causesanimmuneimbalanceinimmunethrombocytopenicpurpurabyreducingthenumberandfunctionoftregcellsthroughtheubiquitinationdegradationofets1 AT shaoyanhu huwe1causesanimmuneimbalanceinimmunethrombocytopenicpurpurabyreducingthenumberandfunctionoftregcellsthroughtheubiquitinationdegradationofets1 AT zhaoyuewang huwe1causesanimmuneimbalanceinimmunethrombocytopenicpurpurabyreducingthenumberandfunctionoftregcellsthroughtheubiquitinationdegradationofets1
_version_	1718405918219042816

HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1

Ejemplares similares