Qingxiang Zeng1, Wenlong Liu1, Renzhong Luo1, Gen Lu2. 1. Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical College, Guangzhou, China. 2. Department of Respiratory Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical College, Guangzhou, China.
Abstract
BACKGROUND: Regulatory T cells (Tregs) play central roles in limiting airway allergic inflammation and preventing inappropriate Th2 responses to environmental allergens. This study aims to evaluate the role of miR-181a and miR-155 in the regulation of the differentiation and function of Tregs through both in vivo and in vitro studies. METHODS: The CD4+ T cells and Tregs were purified from peripheral blood mononuclear cells (PBMCs) in allergic rhinitis (AR) children, respectively. The miR-155/181a mimics and inhibitors were transfected into CD4+ T cells and Tregs. The differentiation and function of Tregs were evaluated by flow cytometry and enzyme-linked immunosorbent assay. AR mice models were established, and miR-155/181a mimics or inhibitors were injected through tail vein. The Treg percentage and function from mice were compared among different groups. RESULTS: The miR-181a up-regulated the release of interleukin (IL)-10 and TGF-β, whereas the miR-155 promoted Treg differentiation in CD4+ T cells. Similarly, we also found that miR-155 promoted Treg proliferation directly through suppressor of cytokine signaling 1 (SOCS1) and sirtuin1 (SIRT1) signaling pathway, whereas miR-181a up-regulated mRNA expression of IL-10 and TGF-β through phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway. We also found that miR-155/181a affect Treg percentage and function in mice model. CONCLUSION: Our findings suggest that miR-181a and miR-155 were closely correlated with the proliferation and function of Tregs in AR, providing new potential treatment target.
BACKGROUND: Regulatory T cells (Tregs) play central roles in limiting airway allergic inflammation and preventing inappropriate Th2 responses to environmental allergens. This study aims to evaluate the role of miR-181a and miR-155 in the regulation of the differentiation and function of Tregs through both in vivo and in vitro studies. METHODS: The CD4+ T cells and Tregs were purified from peripheral blood mononuclear cells (PBMCs) in allergic rhinitis (AR) children, respectively. The miR-155/181a mimics and inhibitors were transfected into CD4+ T cells and Tregs. The differentiation and function of Tregs were evaluated by flow cytometry and enzyme-linked immunosorbent assay. AR mice models were established, and miR-155/181a mimics or inhibitors were injected through tail vein. The Treg percentage and function from mice were compared among different groups. RESULTS: The miR-181a up-regulated the release of interleukin (IL)-10 and TGF-β, whereas the miR-155 promoted Treg differentiation in CD4+ T cells. Similarly, we also found that miR-155 promoted Treg proliferation directly through suppressor of cytokine signaling 1 (SOCS1) and sirtuin1 (SIRT1) signaling pathway, whereas miR-181a up-regulated mRNA expression of IL-10 and TGF-β through phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway. We also found that miR-155/181a affect Treg percentage and function in mice model. CONCLUSION: Our findings suggest that miR-181a and miR-155 were closely correlated with the proliferation and function of Tregs in AR, providing new potential treatment target.
Authors: Mohammad Taheri; Dominik A Barth; Julia Kargl; Omidvar Rezaei; Soudeh Ghafouri-Fard; Martin Pichler Journal: Front Immunol Date: 2021-11-04 Impact factor: 7.561