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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.900243/full |
| _version_ | 1828438249900605440 |
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| author | Na Zhang Fei Wang Gaomeng Zhang Qi Zhang Yuhong Liu Qiao Wang Mohamed Shafey Elsharkawy Maiqing Zheng Jie Wen Guiping Zhao Guiping Zhao Qinghe Li Qinghe Li |
| author_facet | Na Zhang Fei Wang Gaomeng Zhang Qi Zhang Yuhong Liu Qiao Wang Mohamed Shafey Elsharkawy Maiqing Zheng Jie Wen Guiping Zhao Guiping Zhao Qinghe Li Qinghe Li |
| author_sort | Na Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T20:00:13Z |
| format | Article |
| id | doaj.art-9dbb59e0fc33443bb51154969ffb7b14 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T20:00:13Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9dbb59e0fc33443bb51154969ffb7b142022-12-22T01:35:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.900243900243USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responsesNa Zhang0Fei Wang1Gaomeng Zhang2Qi Zhang3Yuhong Liu4Qiao Wang5Mohamed Shafey Elsharkawy6Maiqing Zheng7Jie Wen8Guiping Zhao9Guiping Zhao10Qinghe Li11Qinghe Li12Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest Agriculture and Forestry (A&F) University, Yangling, ChinaKey Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaAnimal Production Department, National Research Centre, Cairo, EgyptKey Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaKey Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaHainan Yazhou Bay Seed Laboratory, Sanya, ChinaKey Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, ChinaHainan Yazhou Bay Seed Laboratory, Sanya, ChinaToll-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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.900243/fullUSP7MyD88deubiquitinasecytokinesinnate immunity |
| spellingShingle | Na Zhang Fei Wang Gaomeng Zhang Qi Zhang Yuhong Liu Qiao Wang Mohamed Shafey Elsharkawy Maiqing Zheng Jie Wen Guiping Zhao Guiping Zhao Qinghe Li Qinghe Li USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses Frontiers in Immunology USP7 MyD88 deubiquitinase cytokines innate immunity |
| 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 | USP7 MyD88 deubiquitinase cytokines innate immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.900243/full |
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