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Article: Human bone marrow mesenchymal stem cell‐derived extracellular vesicles restore Th17/Treg homeostasis in periodontitis via miR‐1246

TitleHuman bone marrow mesenchymal stem cell‐derived extracellular vesicles restore Th17/Treg homeostasis in periodontitis via miR‐1246
Authors
Keywordsextracellular vesicles
microRNA
periodontal disease
stem cell
Issue Date10-Oct-2023
PublisherWiley
Citation
The FASEB Journal, 2023, v. 37, n. 11 How to Cite?
Abstract

T-cell-mediated immunity is crucial in the immunopathology of periodontitis. The restoration of the homeostasis between the T helper cell 17 (Th17) and regulatory T cell (Treg) subsets by extracellular vesicles (EVs) obtained from human bone marrow stem cells (hBMSCs) promotes new bone formation and suppresses inflammation. Uncovering the functions of hBMSC-derived EVs in the immune microenvironment of periodontal tissue and their underlying regulatory mechanisms may shed new light on developing potential cell-free immunotherapies for periodontal regeneration. Here, we reported that the Th17/Treg ratio elevated in peripheral blood from periodontitis patients. Furthermore, we found that hBMSC-derived EVs could reduce the Th17/Treg ratio in CD4+ T cells from periodontitis patients in vitro and ameliorate conditions of experimental periodontitis in mice. Additionally, by investigating the differentially expressed miRNAs and target genes in EVs from hBMSCs stimulated with Porphyromonas gingivalis LPS using miRNA sequencing, we found that EV-miR-1246 is highly effective at downregulating the ratio of Th17/Treg in vitro. Mechanistically, EV-miR-1246 suppressed expression of its potential target angiotensin-converting enzyme 2 (ACE2) and increased the p-Yes-associated protein (YAP)1/YAP1 ratio in CD4+ T cells. Our results indicated that hBMSC-derived EVs improve periodontitis via miR-1246, consequently downregulating Th17/Treg ratio, and represented a promising therapeutic target for precision treatment in periodontitis.


Persistent Identifierhttp://hdl.handle.net/10722/340030
ISSN
2023 Impact Factor: 4.4
2023 SCImago Journal Rankings: 1.412
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXia, Yuxing-
dc.contributor.authorCheng, Tianfan-
dc.contributor.authorZhang, Chengfei-
dc.contributor.authorZhou, Min-
dc.contributor.authorHu, Zhekai-
dc.contributor.authorKang, Feiwu-
dc.contributor.authorLiao, Chongshan-
dc.date.accessioned2024-03-11T10:41:08Z-
dc.date.available2024-03-11T10:41:08Z-
dc.date.issued2023-10-10-
dc.identifier.citationThe FASEB Journal, 2023, v. 37, n. 11-
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/340030-
dc.description.abstract<p>T-cell-mediated immunity is crucial in the immunopathology of periodontitis. The restoration of the homeostasis between the T helper cell 17 (Th17) and regulatory T cell (Treg) subsets by extracellular vesicles (EVs) obtained from human bone marrow stem cells (hBMSCs) promotes new bone formation and suppresses inflammation. Uncovering the functions of hBMSC-derived EVs in the immune microenvironment of periodontal tissue and their underlying regulatory mechanisms may shed new light on developing potential cell-free immunotherapies for periodontal regeneration. Here, we reported that the Th17/Treg ratio elevated in peripheral blood from periodontitis patients. Furthermore, we found that hBMSC-derived EVs could reduce the Th17/Treg ratio in CD4<sup>+</sup> T cells from periodontitis patients in vitro and ameliorate conditions of experimental periodontitis in mice. Additionally, by investigating the differentially expressed miRNAs and target genes in EVs from hBMSCs stimulated with <em>Porphyromonas gingivalis</em> LPS using miRNA sequencing, we found that EV-miR-1246 is highly effective at downregulating the ratio of Th17/Treg in vitro. Mechanistically, EV-miR-1246 suppressed expression of its potential target angiotensin-converting enzyme 2 (ACE2) and increased the p-Yes-associated protein (YAP)1/YAP1 ratio in CD4<sup>+</sup> T cells. Our results indicated that hBMSC-derived EVs improve periodontitis via miR-1246, consequently downregulating Th17/Treg ratio, and represented a promising therapeutic target for precision treatment in periodontitis.<br></p>-
dc.languageeng-
dc.publisherWiley-
dc.relation.ispartofThe FASEB Journal-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectextracellular vesicles-
dc.subjectmicroRNA-
dc.subjectperiodontal disease-
dc.subjectstem cell-
dc.titleHuman bone marrow mesenchymal stem cell‐derived extracellular vesicles restore Th17/Treg homeostasis in periodontitis via miR‐1246-
dc.typeArticle-
dc.identifier.doi10.1096/fj.202300674RR-
dc.identifier.scopuseid_2-s2.0-85173343341-
dc.identifier.volume37-
dc.identifier.issue11-
dc.identifier.eissn1530-6860-
dc.identifier.isiWOS:001081571800001-
dc.identifier.issnl0892-6638-

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