Exosomes Derived from Stem Cells from Apical Papilla Ameliorate Sjogren's Syndrome by Suppressing Th17 Cell Differentiation

Abstract Background: Sjogren's syndrome (SS) is a chronic autoimmune disease that is characterized by progressive lymphocyte infiltration and a decrease in the secretory function of the salivary glands. Mesenchymal stem cell (MSCs) transplantation has shown great potential in the treatment of SS. Exosomes are one of the key paracrine factors that allow MSCs to perform their functions, and are more stable and safer than MSCs. Stem cells from apical papilla (SCAP), a kind of dental stem cells that are derived from the neural crest, have a wide range of immunoregulatory properties. However, the roles of exosomes derived from SCAP (SCAP-Exo) in the treatment of SS are not clear. This study investigated the effects of SCAP-Exo on ameliorating SS and the underlying mechanisms.Methods: SCAP-Exo were isolated and characterized by western blotting, transmission electron microscopy and nanoparticle tracking analysis. SCAP-Exo were systemically infused into SS mice via the tail vein. H&E staining, saliva flow rate tests, flow cytometry and enzyme-linked immunosorbent assays (ELISA) were performed to verify the therapeutic effects of SCAP-Exo. PIWI-interacting RNA (piRNA) array analysis was conducted to determine the piRNA expression profiles of SCAP-Exo, and the key pathways were analysed. A luciferase reporter assay was performed to reveal the molecular role of the exosomal hsa-piR-15254 target interleukin-6 receptor (IL-6R). Furthermore, the molecular mechanism by which hsa-piR-15254 regulated T helper 17 (Th17) cell differentiation in vitro was tested by flow cytometry, ELISA, and reverse transcription-quantitative polymerase chain reaction.Results: We found that SCAP-Exo transplantation successfully improved saliva secretion, alleviated lymphocyte infiltration in the submandibular glands and reduced the proportion of Th17 cells in SS mice. Mechanistically, hsa-piR-15254 was enriched in SCAP-Exo; a luciferase reporter assay demonstrated that hsa-piR-15254 directly targeted the IL-6R mRNA 3’ untranslated region. Furthermore, we revealed that hsa-piR-15254 inhibited Th17 differentiation and downregulated the level of IL-17A in the supernatant and the expression levels of Th17-related genes in vitro.Conclusion: This study demonstrated that SCAP-Exo had a superior therapeutic effect on SS by inhibiting Th17 cell differentiation. These data suggested that SCAP-Exo could be used in a cell-free approach for the clinical treatment of autoimmune disease..

Medienart:	Preprint

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	ResearchSquare.com - (2023) vom: 16. Jan. Zur Gesamtaufnahme - year:2023

Sprache:	Englisch

Beteiligte Personen:	Wang, Aochen [VerfasserIn] Liu, Jie [VerfasserIn] Yu, Si [VerfasserIn] Liu, Xuemei [VerfasserIn] Zhuang, Xueying [VerfasserIn] Liu, Yao [VerfasserIn] Chen, Xu [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	570 Biology

doi:	10.21203/rs.3.rs-864685/v1

funding:
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PPN (Katalog-ID):	XRA033465525