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The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis

Tissue‐infiltrating neutrophils (TINs) secrete various signaling molecules to establish paracrine communication within the inflammatory milieu. It is imperative to identify molecular mediators that control this secretory phenotype of TINs. The present study uncovers a secretory neutrophil subset tha...

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Autores principales: Song, Jia, Zhang, Yuning, Bai, Yunyang, Sun, Xiaowen, Lu, Yanhui, Guo, Yusi, He, Ying, Gao, Min, Chi, Xiaopei, Heng, Boon Chin, Zhang, Xin, Li, Wenjing, Xu, Mingming, Wei, Yan, You, Fuping, Zhang, Xuehui, Lu, Dan, Deng, Xuliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602526/
https://www.ncbi.nlm.nih.gov/pubmed/37639212
http://dx.doi.org/10.1002/advs.202303207
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author Song, Jia
Zhang, Yuning
Bai, Yunyang
Sun, Xiaowen
Lu, Yanhui
Guo, Yusi
He, Ying
Gao, Min
Chi, Xiaopei
Heng, Boon Chin
Zhang, Xin
Li, Wenjing
Xu, Mingming
Wei, Yan
You, Fuping
Zhang, Xuehui
Lu, Dan
Deng, Xuliang
author_facet Song, Jia
Zhang, Yuning
Bai, Yunyang
Sun, Xiaowen
Lu, Yanhui
Guo, Yusi
He, Ying
Gao, Min
Chi, Xiaopei
Heng, Boon Chin
Zhang, Xin
Li, Wenjing
Xu, Mingming
Wei, Yan
You, Fuping
Zhang, Xuehui
Lu, Dan
Deng, Xuliang
author_sort Song, Jia
collection PubMed
description Tissue‐infiltrating neutrophils (TINs) secrete various signaling molecules to establish paracrine communication within the inflammatory milieu. It is imperative to identify molecular mediators that control this secretory phenotype of TINs. The present study uncovers a secretory neutrophil subset that exhibits increased pro‐inflammatory cytokine production and enhanced migratory capacity which is highly related with periodontal pathogenesis. Further analysis identifies the OTU domain‐containing protein 1 (OTUD1) plays a regulatory role in this secretory neutrophil polarization. In human and mouse periodontitis, the waning of inflammation is correlated with OTUD1 upregulation, whereas severe periodontitis is induced when neutrophil‐intrinsic OTUD1 is depleted. Mechanistically, OTUD1 interacts with SEC23B, a component of the coat protein II complex (COPII). By removing the K63‐linked polyubiquitin chains on SEC23B Lysine 81, the deubiquitinase OTUD1 negatively regulates the COPII secretory machinery and limits protein ER‐to‐Golgi trafficking, thus restricting the surface expression of integrin‐regulated proteins, CD9 and CD47. Accordingly, blockade of protein transport by Brefeldin A (BFA) curbs recruitment of Otud1‐deficient TINs and attenuates inflammation‐induced alveolar bone destruction. The results thus identify OTUD1 signaling as a negative feedback loop that limits the polarization of neutrophils with secretory phenotype and highlight the potential application of BFA in the treatment of periodontal inflammation.
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spelling pubmed-106025262023-10-27 The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis Song, Jia Zhang, Yuning Bai, Yunyang Sun, Xiaowen Lu, Yanhui Guo, Yusi He, Ying Gao, Min Chi, Xiaopei Heng, Boon Chin Zhang, Xin Li, Wenjing Xu, Mingming Wei, Yan You, Fuping Zhang, Xuehui Lu, Dan Deng, Xuliang Adv Sci (Weinh) Research Articles Tissue‐infiltrating neutrophils (TINs) secrete various signaling molecules to establish paracrine communication within the inflammatory milieu. It is imperative to identify molecular mediators that control this secretory phenotype of TINs. The present study uncovers a secretory neutrophil subset that exhibits increased pro‐inflammatory cytokine production and enhanced migratory capacity which is highly related with periodontal pathogenesis. Further analysis identifies the OTU domain‐containing protein 1 (OTUD1) plays a regulatory role in this secretory neutrophil polarization. In human and mouse periodontitis, the waning of inflammation is correlated with OTUD1 upregulation, whereas severe periodontitis is induced when neutrophil‐intrinsic OTUD1 is depleted. Mechanistically, OTUD1 interacts with SEC23B, a component of the coat protein II complex (COPII). By removing the K63‐linked polyubiquitin chains on SEC23B Lysine 81, the deubiquitinase OTUD1 negatively regulates the COPII secretory machinery and limits protein ER‐to‐Golgi trafficking, thus restricting the surface expression of integrin‐regulated proteins, CD9 and CD47. Accordingly, blockade of protein transport by Brefeldin A (BFA) curbs recruitment of Otud1‐deficient TINs and attenuates inflammation‐induced alveolar bone destruction. The results thus identify OTUD1 signaling as a negative feedback loop that limits the polarization of neutrophils with secretory phenotype and highlight the potential application of BFA in the treatment of periodontal inflammation. John Wiley and Sons Inc. 2023-08-28 /pmc/articles/PMC10602526/ /pubmed/37639212 http://dx.doi.org/10.1002/advs.202303207 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Song, Jia
Zhang, Yuning
Bai, Yunyang
Sun, Xiaowen
Lu, Yanhui
Guo, Yusi
He, Ying
Gao, Min
Chi, Xiaopei
Heng, Boon Chin
Zhang, Xin
Li, Wenjing
Xu, Mingming
Wei, Yan
You, Fuping
Zhang, Xuehui
Lu, Dan
Deng, Xuliang
The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis
title The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis
title_full The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis
title_fullStr The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis
title_full_unstemmed The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis
title_short The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis
title_sort deubiquitinase otud1 suppresses secretory neutrophil polarization and ameliorates immunopathology of periodontitis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602526/
https://www.ncbi.nlm.nih.gov/pubmed/37639212
http://dx.doi.org/10.1002/advs.202303207
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