miR-155 antagomir protect against DSS-induced colitis in mice through regulating Th17/Treg cell balance by Jarid2/Wnt/?-catenin - 19/04/20
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Graphical abstract |
Mechanism of miR-155 regulating T cell differentiation through Jarid2/Wnt/β-catenin pathway
Highlights |
• | miR-155 antagomir can relieve DSS-induced colitis. |
• | miR-155 antagomir can regulate Th17/Treg cell balance of UC intestinal mucosa. |
• | miR-155 antagomir may regulate UC intestinal mucosal immune function through Jarid2/Wnt/β-catenin pathway. |
Abstract |
Background |
Th subsets particularly T helper 17 and regulatory T cells play a critical role in immune balance in colonic mucosa of Inflammatory Bowel Disease. Recent studies have indicated miR-155 is overexpressed in the colonic mucosa in IBD patients. Thus, whether and how miR-155 influences Th17/Treg cell balance in IBD patients is worthy of researching.
Methods |
We divided mice into four groups: the mice oral administration of 3.0 % DSS in fresh drinking water for 7 days except normal group. In this period, starting from the fifth day, the miR-155 and NC antagomir group were carried out by intraperitoneal injection of miR-155 antagomirs and corresponding negative controls. In vitro, we isolated naïve CD4+T cells and divided into two groups: the cells were transfected with mmu-miR-155-5p inhibitor or corresponding negative controls and then induced differentiation.
Results |
We found miR-155 antagomir can reach colon tissues in DSS-induced colitis and indeed ameliorated DSS-induced experimental colitis. Subsequently, we proved the levels of Th17 cells in spleens and Mesenteric lymph nodes and its associated IL-6, IL-17A and RORγt in colonic tissues were dramatically decreased and TGF-β1 raised in DSS + miR-155 antagomir group. However, miR-155 antagomir significantly increased the expression of Tregs. In vitro, we found miR-155 inhibitor could improve the Tregs but decrease Th17 cells. Finally, we dig out that Jarid2 was apparently improved by miR-155 antagomir, Wnt/β-catenin and its associated T cell factor-4 (TCF-4) and Cyclin D1 expression were positively correlated with Jarid2.
Conclusion |
Silencing of miR-155 attenuates DSS-induced colitis by regulating Th17/Treg cell balance and Jarid2/Wnt/β-catenin participated in the process.
Le texte complet de cet article est disponible en PDF.Keywords : miR-155 antagomir, IBD, Th17/Treg cell balance, Jarid2, Wnt/β-catenin
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Article 109909- juin 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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