MiR-29b regulates Th2 cell differentiation in asthma by targeting inducible B7-H3 and STAT3.
MiR-29b regulates Th2 cell differentiation in asthma by targeting inducible B7-H3 and STAT3.
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MiR-29b 通过靶向诱导型 B7-H3 和 STAT3 调节哮喘中的 Th2 细胞分化
DOI：
10.1002/clt2.12114
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发表时间：
2022-01
影响因子：
4.4
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Gu W;Li G;Zhang W;Zhang X;He Y;Huang L;Yan Y;Ji W;Hao C;Chen Z
MicroRNA在T细胞应答中起重要作用。然而，microRNA如何调节哮喘中的Th细胞仍然不清楚。本研究旨在探讨miR-29 b调控哮喘Th细胞的机制和途径，以期为哮喘的治疗寻找新的靶点。我们检测了哮喘患儿外周血中的miR-29 b、B7-H3和STAT 3，通过体外细胞培养探讨了这些分子之间的关系及其对T细胞的影响，并通过动物模型进行了验证。哮喘儿童外周血单个核细胞中miR-29 b水平降低。体外研究发现，屋尘螨（HDM）刺激后，巨噬细胞中miR-29 b的表达降低，B7-H3和STAT 3的表达增加。巨噬细胞中miR-29 b下调后，巨噬细胞中B7-H3和STAT 3的表达增加，T细胞分化为Th 2细胞。加入B7-H3或STAT 3抗体后，幼稚T细胞向Th 2细胞的分化减少。在OVA诱导的小鼠哮喘模型中，肺组织中miR-29 b上调后，小鼠肺组织中B7-H3和STAT 3的表达降低，同时Th 2细胞和II型细胞因子的表达降低。肺组织病理改变减轻。miR-29 b在哮喘儿童中的表达降低。MiR-29 b可通过同时抑制B7-H3和STAT 3通路，抑制Th 2细胞分化，减轻哮喘免疫炎症。
MicroRNAs play an important role in T cell responses. However, how microRNAs regulate Th cells in asthma remains poorly defined. In this study, we investigated the mechanism and pathways of miR‐29b regulating Th cells in asthma, in order to find new targets for asthma. We detected miR‐29b, B7‐H3 and STAT3 in the peripheral blood of children with asthma, explored the relationship between these molecules and their effects on T cells through in vitro cell culture, and verified it by animal model. MiR‐29b levels were decreased in the peripheral blood mononuclear cells from children with asthma. Vitro studies found that the expression of miR‐29b in macrophages was decreased and the expression of B7‐H3 and STAT3 was increased after house dust mite (HDM) stimulation. After down‐regulation of miR‐29b in macrophages, the expressions of B7‐H3 and STAT3 in macrophages were increased and T cells differentiate into Th2 cells. After the addition of B7‐H3 or STAT3 antibodies, the differentiation of naive T cells into Th2 cells was reduced. In OVA induced mice asthmatic model, after the up‐regulation of miR‐29b in lung, the expression of B7‐H3 and STAT3 decreased in the lung tissues of mice, and the expression of Th2 cells and type II cytokine decreased simultaneously. The pathological changes of lung tissues were also alleviated. The expression of miR‐29b is decreased in asthmatic children. MiR‐29b can inhibit Th2 cell differentiation by inhibiting B7‐H3 and STAT3 pathways at the same time, and reduce asthmatic immune inflammation.
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