Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion

2012 ◽  
Vol 40 (9) ◽  
pp. 761-770 ◽  
Author(s):  
Xuebin Qu ◽  
Xingxia Liu ◽  
Kai Cheng ◽  
Rongcun Yang ◽  
Robert C.H. Zhao
2013 ◽  
Vol 191 (11) ◽  
pp. 5777-5777 ◽  
Author(s):  
Soufiane Ghannam ◽  
Jérôme Pène ◽  
Gabriel Moquet-Torcy ◽  
Christian Jorgensen ◽  
Hans Yssel

2010 ◽  
Vol 185 (1) ◽  
pp. 302-312 ◽  
Author(s):  
Soufiane Ghannam ◽  
Jérôme Pène ◽  
Gabriel Torcy-Moquet ◽  
Christian Jorgensen ◽  
Hans Yssel

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Ruili Yang ◽  
Huaming Huang ◽  
Shengjie Cui ◽  
Yikun Zhou ◽  
Ting Zhang ◽  
...  

Abstract Bone marrow mesenchymal stem cells (MSCs) have demonstrated therapeutic effects for colitis through immunomodulation and anti-inflammation. However, whether MSC-derived exosomes possessed the similar function remains unclear. In present study, exosomes were isolated from control and IFN-γ-primed MSCs and was verified by transmission electron microscope (TEM) and immunofluorescence staining. Administration of exosomes to mice significantly improved the disease activity index and histological score of colitis, and decreased the ratio of Th17 cells with elevated Treg cells ratio in mice colitis model. Exosomes from IFN-γ-primed MSCs showed superior therapeutic effects to colitis. Exosomes treatment inhibited Th17 differentiation in vitro, and exosomes from IFN-γ-primed MSCs showed higher inhibition efficacy. Mechanistically, exosomes treatment significantly decreased the expression of Stat3 and p-Stat3 to inhibit Th17 cells differentiation. IFN-γ pretreatment increased the level of miR-125a and miR-125b of exosomes, which directly targeted on Stat3, to repress Th17 cell differentiation. Moreover, combination of miR-125a and miR-125b agmior infusion also showed therapeutic effects for colitis, accompanied by decreased Th17 cell ratio. Collectively, this study demonstrates that IFN-γ treatment promoted exosomes from MSCs to attenuate colitis through increasing the level of miR-125a and miR-125b, which binding on 3′-UTR of Stat3 to repress Th17 cell differentiation. This study provides a new approach of exocytosis on the treatment of colitis.


2021 ◽  
Author(s):  
Aochen Wang ◽  
Jie Liu ◽  
Si Yu ◽  
Xuemei Liu ◽  
Xueying Zhuang ◽  
...  

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.


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