Feng Zhu1, Huarong Li1, Yujin Liu1, Chen Tan1, Xingxing Liu1, Heng Fan2, Hui Wu1, Yalan Dong1, Ting Yu1, Si Chu1, Hongxia He1, Xiwen Zhu1. 1. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. 2. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: fanheng009@aliyun.com.
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.
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 IBDpatients. Thus, whether and how miR-155 influences Th17/Treg cell balance in IBDpatients 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.
Authors: Kanika Suri; Jason A Bubier; Michael V Wiles; Leonard D Shultz; Mansoor M Amiji; Vishnu Hosur Journal: Cells Date: 2021-08-26 Impact factor: 7.666