He Shaojun, Zhou Jingrun, Ma Ying, Wang Wei, Yang Jiong
Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, China.
Inflammation. 2023 Feb;46(1):370-387. doi: 10.1007/s10753-022-01739-5. Epub 2022 Sep 16.
Disruption of T-cell differentiation is characteristic of airway inflammation in allergic asthma. How miR-19a works in asthma has not been completely elucidated. This study aimed to examine whether microRNA-19a regulates helper T-cell proliferation and to identify the factors involved and the underlying mechanisms. Our results showed that miR-19a levels were upregulated in parallel with a reduction in RUNX3 expression in a house dust mite (HDM)-induced murine model of asthma. A dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay showed that RUNX3 was a direct target of miR-19a. Inhibiting the expression of miR-19a attenuated inflammation and mucus production, induced Th1 cells, suppressed the Th2 inflammatory response, and repressed dendritic cell (DC) maturation by increasing RUNX3 expression in WT asthmatic mice but not RUNX3 mice. In vitro experiments revealed that miR-19a inhibition could target RUNX3 to induce Th1 polarization and inhibit Th2 polarization by directly acting on naïve CD4 T cells or indirectly mediating the maturation and antigen-presenting abilities of DCs. These findings indicate that miR-19a directly and indirectly regulates immunoinflammatory responses in asthma by targeting RUNX3.
T细胞分化的破坏是过敏性哮喘气道炎症的特征。miR-19a在哮喘中的作用机制尚未完全阐明。本研究旨在探讨微小RNA-19a是否调节辅助性T细胞增殖，并确定相关因素及潜在机制。我们的结果表明，在屋尘螨（HDM）诱导的哮喘小鼠模型中，miR-19a水平上调，同时RUNX3表达降低。双荧光素酶报告基因检测和RNA免疫沉淀（RIP）检测表明，RUNX3是miR-19a的直接靶点。抑制miR-19a的表达可减轻炎症和黏液分泌，诱导Th1细胞，抑制Th2炎症反应，并通过增加野生型哮喘小鼠而非RUNX3基因敲除小鼠的RUNX3表达来抑制树突状细胞（DC）成熟。体外实验表明，抑制miR-19a可通过直接作用于初始CD4 T细胞或间接调节DC的成熟和抗原呈递能力，靶向RUNX3诱导Th1极化并抑制Th2极化。这些发现表明，miR-19a通过靶向RUNX3直接和间接调节哮喘中的免疫炎症反应。
