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USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses

Toll-like receptors (TLRs) are involved in the sensing of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, unmethylated double-stranded DNA (CpG), single-stranded RNA (ssRNA) and lipoproteins. Myeloid differentiation primary response protein 88 (MyD88) is a...

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Autores principales: Zhang, Na, Wang, Fei, Zhang, Gaomeng, Zhang, Qi, Liu, Yuhong, Wang, Qiao, Elsharkawy, Mohamed Shafey, Zheng, Maiqing, Wen, Jie, Zhao, Guiping, Li, Qinghe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412818/
https://www.ncbi.nlm.nih.gov/pubmed/36032091
http://dx.doi.org/10.3389/fimmu.2022.900243
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author Zhang, Na
Wang, Fei
Zhang, Gaomeng
Zhang, Qi
Liu, Yuhong
Wang, Qiao
Elsharkawy, Mohamed Shafey
Zheng, Maiqing
Wen, Jie
Zhao, Guiping
Li, Qinghe
author_facet Zhang, Na
Wang, Fei
Zhang, Gaomeng
Zhang, Qi
Liu, Yuhong
Wang, Qiao
Elsharkawy, Mohamed Shafey
Zheng, Maiqing
Wen, Jie
Zhao, Guiping
Li, Qinghe
author_sort Zhang, Na
collection PubMed
description Toll-like receptors (TLRs) are involved in the sensing of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, unmethylated double-stranded DNA (CpG), single-stranded RNA (ssRNA) and lipoproteins. Myeloid differentiation primary response protein 88 (MyD88) is a canonical adaptor for the Toll-like receptor family which has crucial roles in host defense against infection by microbial pathogens. The dysregulation of MyD88 may also induce autoimmune diseases. Here, we demonstrate that the deubiquitinase USP7 interacts with MyD88 in chicken, with knockdown or overexpression of USP7 leading to the regulation of MyD88 protein in a positive manner. Consequently, USP7 positively regulates the expression of proinflammatory factors upon LPS challenge. Furthermore, we observed USP7-deficient mice to be more susceptible to infection by Salmonella typhimurium. Collectively, our findings demonstrate MyD88 as a bona fide substrate of USP7 and uncover a mechanism by which USP7 regulates innate immune signaling.
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spelling pubmed-94128182022-08-27 USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses Zhang, Na Wang, Fei Zhang, Gaomeng Zhang, Qi Liu, Yuhong Wang, Qiao Elsharkawy, Mohamed Shafey Zheng, Maiqing Wen, Jie Zhao, Guiping Li, Qinghe Front Immunol Immunology Toll-like receptors (TLRs) are involved in the sensing of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, unmethylated double-stranded DNA (CpG), single-stranded RNA (ssRNA) and lipoproteins. Myeloid differentiation primary response protein 88 (MyD88) is a canonical adaptor for the Toll-like receptor family which has crucial roles in host defense against infection by microbial pathogens. The dysregulation of MyD88 may also induce autoimmune diseases. Here, we demonstrate that the deubiquitinase USP7 interacts with MyD88 in chicken, with knockdown or overexpression of USP7 leading to the regulation of MyD88 protein in a positive manner. Consequently, USP7 positively regulates the expression of proinflammatory factors upon LPS challenge. Furthermore, we observed USP7-deficient mice to be more susceptible to infection by Salmonella typhimurium. Collectively, our findings demonstrate MyD88 as a bona fide substrate of USP7 and uncover a mechanism by which USP7 regulates innate immune signaling. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9412818/ /pubmed/36032091 http://dx.doi.org/10.3389/fimmu.2022.900243 Text en Copyright © 2022 Zhang, Wang, Zhang, Zhang, Liu, Wang, Elsharkawy, Zheng, Wen, Zhao and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Na
Wang, Fei
Zhang, Gaomeng
Zhang, Qi
Liu, Yuhong
Wang, Qiao
Elsharkawy, Mohamed Shafey
Zheng, Maiqing
Wen, Jie
Zhao, Guiping
Li, Qinghe
USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses
title USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses
title_full USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses
title_fullStr USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses
title_full_unstemmed USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses
title_short USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses
title_sort usp7 promotes deubiquitination and stabilization of myd88 to enhance immune responses
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412818/
https://www.ncbi.nlm.nih.gov/pubmed/36032091
http://dx.doi.org/10.3389/fimmu.2022.900243
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