MicroRNA‐181a and microRNA‐155 are involved in the regulation of the differentiation and function of regulatory T cells in allergic rhinitis children

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.

MicroRNAs Regulate Intestinal Immunity and Gut Microbiota for Gastrointestinal Health: A Comprehensive Review

“…MiR-155 can regulate Th17/T reg cell balance by inhibiting cytotoxic T-lymphocyte-associated protein 4 expressions, and the overexpression of miR-155 reduces follicular T reg cells, while central T reg cells and miR-155-5p further target sirtuin-1 to maintain the balance of Th17/T reg cells [ 80 ]. Furthermore, miR-122a, miR-146a, miR-155, and miR-181a are highly expressed in T cells, with a close connection with T reg cells, which can target interferon regulatory factor 4 for suppressing IL-6 secretion and inducing IL-17A production, thus assisting in the mitigation of IBD [ 81 , 82 , 83 , 84 ]. In addition, the overexpression of miR-125a can inhibit the differentiation of CD4 + T cells into either Th1 or Th17 cells, which also contributes to immune-regulation [ 85 ].…”

The Role of MicroRNAs in Regulatory T Cells

“…The mRNA levels of IL-10 and TGF-βin peripheral blood mononuclear cells (PBMCs) of allergic rhinitis (AR) mice treated with micro181a mimics were higher than those of AR mice treated with micro181a inhibitors. These studies showed that micro181a regulated the suppressive function of Tregs in vitro and vivo[63].…”

Bisphenol A Exacerbates Allergic Inflammation in an Ovalbumin-Induced Mouse Model of Allergic Rhinitis

“…Treg prevents inappropriate Th2 responses to environmental allergens [ 3 , 31 ]. Th2 cells secrete inhibitory cytokines, including IL-10, that induce Treg formation from naive T cells and inhibit the development of other types of immune cells [ 32 ].…”

“…AR affects over 500 million people worldwide [ 1 , 2 ]. Regulatory T cells (Tregs) play an important role in preventing Th2-mediated inappropriate responses to environmental allergens [ 3 ]. In recent years, the morbidity rate of AR has raised, especially among preschool children [ 4 – 6 ].…”