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  • Title: Administration of a microRNA-21 inhibitor improves the lupus-like phenotype in MRL/lpr mice by repressing Tfh cell-mediated autoimmune responses.
    Author: Gao X, Song Y, Du P, Yang S, Cui H, Lu S, Hu L, Liu L, Jia S, Zhao M.
    Journal: Int Immunopharmacol; 2022 May; 106():108578. PubMed ID: 35124415.
    Abstract:
    BACKGROUND: Inhibiting Tfh cell overexpansion prevents autoimmune responses and disease flares in systemic lupus erythematosus (SLE). miR-21 is highly expressed in SLE CD4+ T cells, but whether inhibiting miR-21 can reduce Tfh cell expansion and alleviate the disease progression of lupus is unclear. AIM OF THE STUDY: To address the role and molecular mechanism of miR-21 in regulating Tfh cell expansion and its therapeutic effect on SLE. METHODS: We treated 12-week-old MRL/lpr mice with Antagomir-21, which specifically inhibited miR-21 in vivo. After 12 weeks of treatment, we examined the proportions of Tfh cells and germinal center (GC) B cells and serum levels of autoantibodies and evaluated disease severity by histological scoring and albuminuria. We determined the level of intracellular free iron in CD4+ T cells by PGSK probe and examined the expression of the Fth and Tfrc genes by qPCR. Immunohistochemistry (IHC)was used to assess the 5-hmC level in the draining lymph nodes (dLNs) and spleen. RESULTS AND CONCLUSIONS: Inhibiting miR-21 significantly reduced the expansion of Tfh cells and GC B cells. Furthermore, Antagomir-21 highly improved skin lesions and nephritis in MRL/lpr mice. Inhibiting miR-21 reduced intracellular iron accumulation and DNA hydroxymethylation in T cells. In conclusion, inhibiting miR-21 in vivo improves intracellular iron homeostasis and inhibits Tfh cell overexpansion, contributing to reduced autoimmune responses and the remission of disease symptoms in murine lupus.
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