MicroRNA-181a regulates Treg functions via TGF-β1/Smad axis in the spleen of mice with acute gouty arthritis induced by MSU crystals

Abstract

Regulatory T cells (Tregs) play critical roles in restricting inflammatory pathogenesis and limiting undesirable Th2 response to environmental allergens. However, the role of miR-181a in regulating acute gouty arthritis (AGA) and Treg function remains unclear. This study aimed to investigate the potential roles of miR-181a in Treg immunity and the associated signaling pathway in the AGA mouse model. A solution with monosodium urate (MSU) crystals was injected into the joint tissue of mice to induce AGA. ELISA was used to examine inflammatory factors in blood samples, and flow cytometry was used to analyze Treg profile in mice with MSU-induced AGA. Cell proliferation and viability were assessed by CCK-8 assay. TGF-β1/Smad signaling activation was detected by western blot. We found that miR-181a expression showed a positive correlation with the changes of splenic Tregs percentage in AGA mice. miR-181a regulated the TGF-β1/Smad axis, since the transfection of miR-181a mimic increased the level of TGF-β1 and the phosphorylation of Smad2/3 in Tregs in AGA mice. Additionally, miR-181a mimic also promoted responses of Tregs via TGF-β1 in vitro and in vivo . Our work uncovered a vital role of miR-181a in the immune function of Treg cells by mediating the activity of the TGF-β1/Smad pathway in the AGA mouse model induced by MSU.

CD4+ T-cell subsets in autoimmune hepatitis: A review

“…As mentioned, TGF-β participates in Treg differentiation. Tregs produce TGF-β, which can upregulate Foxp3 expression through the TGF-β-Smad pathway and establish positive feedback to support Treg differentiation 133 ; IL-10 inhibits various cytokines, such as IL-2, IFN-γ, and GM-CSF, to inhibit Th1 and Th17 differentiation. 134 , 135 Treg cells highly express the inhibitory receptor CTLA-4, which plays an important role in immunosuppression.…”