DataVXAdvanced SciencePaper
journal article·2023-10Open access

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

Jia Song, Yuning Zhang, Yunyang Bai, Xiaowen Sun, Yanhui Lu, Yusi Guo, Ying He, Min Gao, Xiaopei Chi, Boon Chin Heng, Xin Zhang, Wenjing Li, Mingming Xu, Yan Wei, Fuping You, Xuehui Zhang, Dan Lu, Xuliang Deng

Advanced Science· Volume 10· Issue 30
Publisher pageOpen full text
Source abstract

Abstract

Abstract 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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Neutrophil, Myeloperoxidase and Oxidative Mechanisms · Cell Adhesion Molecules Research · Immune Response and Inflammation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081 P. R. China

Department of Dental Materials & Dental Medical Devices Testing Center Peking University School and Hospital of Stomatology Beijing 100081 P. R. China

National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Research Center of Oral Biomaterials and Digital Medical Devices NMPA Key Laboratory for Dental Materials Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology Beijing 100081 P. R. China

Department of Orthodontics Peking University School and Hospital of Stomatology Beijing 100081 P. R. China

Central Laboratory Peking University School and Hospital of Stomatology Beijing 100081 P. R. China

Institute of Systems Biomedicine School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Beijing Key Laboratory of Tumor Systems Biology Peking University Health Science Center Beijing 100191 P. R. China

Peking University‐Yunnan Baiyao International Medical Research Center Beijing 100191 P. R. China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · China Postdoctoral Science Foundation · Natural Science Foundation of Beijing Municipality

References (36)

Show source-provided references
1. 10.1126/science.abl545010.1126/science.abl5450 ↗
2. 10.1111/prd.1231310.1111/prd.12313 ↗
3. Van Bruggen S. · Immunol Rev · 2022
4. 10.1182/blood-2018-11-84454810.1182/blood-2018-11-844548 ↗
5. 10.1038/s41568-020-0281-y10.1038/s41568-020-0281-y ↗
6. 10.3390/biomedicines909123610.3390/biomedicines9091236 ↗
7. 10.1111/tra.1265410.1111/tra.12654 ↗
8. 10.1038/ng187610.1038/ng1876 ↗
9. 10.1038/ng.40510.1038/ng.405 ↗
10. 10.1038/nrm309910.1038/nrm3099 ↗
11. 10.1038/nature1082210.1038/nature10822 ↗
12. 10.1016/j.cell.2013.05.04610.1016/j.cell.2013.05.046 ↗
13. 10.1038/s41423-021-00810-910.1038/s41423-021-00810-9 ↗
14. 10.1016/j.jaut.2018.07.01910.1016/j.jaut.2018.07.019 ↗
15. 10.4049/jimmunol.190030510.4049/jimmunol.1900305 ↗
16. 10.1038/s41467-022-34654-210.1038/s41467-022-34654-2 ↗
17. 10.15252/embr.20205116210.15252/embr.202051162 ↗
18. 10.1016/j.cell.2021.05.01310.1016/j.cell.2021.05.013 ↗
19. 10.1111/prd.1222110.1111/prd.12221 ↗
20. 10.1016/j.cell.2022.01.01010.1016/j.cell.2022.01.010 ↗
21. 10.1002/eji.20134419510.1002/eji.201344195 ↗
22. 10.1371/journal.pntd.001022410.1371/journal.pntd.0010224 ↗
23. 10.1073/pnas.120920710910.1073/pnas.1209207109 ↗
24. 10.1182/blood.201900094810.1182/blood.2019000948 ↗
25. 10.3324/haematol.2013.08552210.3324/haematol.2013.085522 ↗
26. 10.7554/eLife.4225310.7554/eLife.42253 ↗
27. 10.1038/nrm358810.1038/nrm3588 ↗
28. 10.1016/j.bbamcr.2013.02.00310.1016/j.bbamcr.2013.02.003 ↗
29. 10.1172/JCI13657410.1172/JCI136574 ↗
30. 10.1136/jitc-2021-00244310.1136/jitc-2021-002443 ↗
31. 10.3390/jcm808113510.3390/jcm8081135 ↗
32. 10.1111/j.1600-051X.2009.01393.x10.1111/j.1600-051X.2009.01393.x ↗
33. 10.1038/s41467-022-34885-310.1038/s41467-022-34885-3 ↗
34. 10.1038/s41419-020-2358-710.1038/s41419-020-2358-7 ↗
35. 10.1002/advs.20220634410.1002/advs.202206344 ↗
36. 10.1038/nmeth.192810.1038/nmeth.1928 ↗