Mycobacterium Vaccae Regulate γδT17 and γδTreg Cells in Mice Asthmatic Lung.

Yien Yao, Xiaoju Chen, Caicheng Qin, Jianlin Huang, Siyue Xu, Chaoqian Li
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Abstract

Background Dysregulation of the balance between different T cell populations is believed to be an important basis for asthma.Objective To observe the changes in γδT subtypes in transgenic asthmatic mice after aerosol inhalation of Mycobacterium vaccae, and to further investigate the mechanism of M. vaccae in asthmatic mice and its relationship with γδT cells.Methods TCR-β-/- mice were exposed to atomized normal saline or M. vaccae for 5 days and the γδT cells from the lung tissues were isolated. Changes in γδT17 and γδTreg populations were detected. Asthma was induced in BALB/c mice using ovalbumin, which was then transplanted with control or M. vaccae-primed γδT cells. First we analyzed the content of γδT cells that secrete IL-17 (IL-17 γδT cells) and Foxp3+ γδT cells in lung tissues and then measured the content of IL-17 in the bronchoalveolar lavage fluid (BALF) by ELISA.Results Exposure to M. vaccae increased and decreased the relative proportions of Foxp3+ γδT cells and IL-17+ γδT cells, respectively, thereby decreasing airway reactivity and inflammation levels in asthmatic mice, and significantly decreasing IL-17 levels in BALF. Furthermore, mice treated with these primed T cells showed a decrease in IL-17+ γδT cells, and a concomitant increase in Foxp3+ γδT cells in their lung tissues. Furthermore, adoptive transfer of M. vaccae-primed γδT cells decreased GATA3 and NICD and increased T-bet in lung.Conclusions The M. vaccae-primed γδT cells alleviated the symptoms of asthma by reversing Th2 polarization in the lungs and inhibiting the Notch/GATA3 pathway.

母牛分枝杆菌对哮喘小鼠肺中γδT17和γδTreg细胞的调节作用
不同T细胞群之间的平衡失调被认为是哮喘的重要基础。目的观察雾化吸入母牛分枝杆菌后转基因哮喘小鼠体内γδT亚型的变化,进一步探讨母牛分枝杆菌在哮喘小鼠体内的作用机制及其与γδT细胞的关系。方法将TCR-β-/-小鼠分别雾化生理盐水或母牛分枝杆菌培养5 d,分离肺组织γδT细胞。检测γδT17和γδTreg居群的变化。用卵清蛋白诱导BALB/c小鼠哮喘,然后将卵清蛋白与对照或M. vaccae引物γδT细胞移植。首先分析肺组织中分泌IL-17的γδT细胞(IL-17 γδT细胞)和Foxp3+ γδT细胞的含量,然后用ELISA法测定支气管肺泡灌洗液(BALF)中IL-17的含量。结果母牛分枝杆菌暴露使哮喘小鼠的Foxp3+ γδT细胞和IL-17+ γδT细胞的相对比例分别升高和降低,从而降低气道反应性和炎症水平,显著降低BALF中IL-17的水平。此外,用这些T细胞处理的小鼠肺组织中IL-17+ γδT细胞减少,Foxp3+ γδT细胞增加。此外,母牛芽胞杆菌引物γδT细胞过继性转移可降低GATA3和NICD,增加肺T-bet。结论母牛分枝杆菌引发的γδT细胞通过逆转肺部Th2极化和抑制Notch/GATA3通路减轻哮喘症状。
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