Recovery from acute lung injury can be regulated via modulation of regulatory T cells and Th17 cells
Recovery from acute lung injury can be regulated via modulation of regulatory T cells and Th17 cells
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DOI：
10.1111/sji.12715
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发表时间：
2018-09
影响因子：
3.7
通讯作者：
Linlin Wang;Xiaocen Wang;L. Tong;Jian Wang;Maosen Dou;Shimeng Ji;J. Bi;Cuicui Chen;Dong Yang-Do
中科院分区：
文献类型：
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作者：
Linlin Wang;Xiaocen Wang;L. Tong;Jian Wang;Maosen Dou;Shimeng Ji;J. Bi;Cuicui Chen;Dong Yang-Do
急性肺损伤（acute lung injury，ALI）是一种严重的炎症性疾病，目前尚无特效治疗方法.调节性T细胞（CD 4 + CD 25 + FoxP 3 T细胞）和Th 17细胞的比例降低与ALI和炎症有关。本研究旨在探讨维持CD 4 + CD 25 + Foxp 3 + T细胞和Th 17细胞的平衡是否可以减轻肺损伤。对于CD 4 + CD 25 + FoxP 3 Treg耗竭，在脂多糖（LPS）滴注前的第-3天和第-1天，每只小鼠腹膜内施用200 μg抗CD 25抗体。在LPS滴注后第0天，每只小鼠腹膜内施用150 μg TGF-β。为了下调Thl 7细胞，在LPS滴注后第0天，将每只小鼠200 μg同种型IL-17或IL-22抗体腹膜内注射到小鼠中。检测肺组织形态学;肺湿干重比;支气管肺泡灌洗液（BALF）中的蛋白浓度、总细胞、中性粒细胞和巨噬细胞计数以及细胞因子。检测肺组织中CD 4 + CD 25 + Foxp 3 + T淋巴细胞百分率和Th 17细胞百分率。通过抗-CD 25治疗或TGF-β中和的CD 4 + CD 25 + Foxp 3 + Tcl 3耗竭延迟了ALI的恢复。持续性炎症主要由中性粒细胞、巨噬细胞和Th 17细胞主导。此外，通过抗IL-17和IL-22的单克隆抗体抑制Th 17细胞，通过抑制中性粒细胞和巨噬细胞的募集，增加CD 4 + CD 25 + Foxp 3 + T细胞的数量，减轻了ALI炎症。我们的研究结果支持了CD 4 + CD 25 + Foxp 3 + T细胞在调节ALI病理生理中的关键作用，以及在ALI治疗中抑制Th 17细胞的潜在治疗作用。这些发现为通过调节CD 4 + CD 25 + Foxp 3 + T细胞和Th 17细胞治疗ALI患者提供了理论基础。
Acute lung injury (ALI) is a severe inflammatory disease, for which no specific treatment exists. The decreased ratio of regulatory T cells (CD4+CD25+FoxP3 Tregs) and Th17 cells is implicated in ALI and inflammation. We here investigated whether maintaining the balance of CD4+CD25+Foxp3+Tregs and Th17 cells can alleviate lung injury. For CD4+CD25+FoxP3 Treg depletion, 200 μg of an anti‐CD25 antibody was administered intraperitoneally per mouse on days −3 and −1 before lipopolysaccharide (LPS) instillation. And 150 μg of TGF‐β was administered intraperitoneally per mouse on day 0 after LPS instillation. To down‐regulate of Th17 cells, 200 μg per mouse of isotype, IL‐17 or IL‐22 antibodies were injected intraperitoneally into mice at days 0 after LPS instillation. We detected lung morphology; lung wet‐to‐dry weight ratio; protein concentration, the count of total cells, neutrophils and macrophages, and cytokines in bronchoalveolar lavage fluid (BALF). And we also evaluated the percentage of CD4+CD25+Foxp3+Tregs in lung, and Th17 cells in lung. CD4+CD25+Foxp3+Tregs depletion via anti‐CD25 treatment or TGF‐β neutralization delayed recovery of ALI. The prolonged inflammation was mainly dominated by neutrophils, macrophages and Th17 cells. Furthermore, inhibition of Th17 cells via monoclonal antibodies against IL‐17 and IL‐22 alleviated ALI inflammation by inhibiting the recruitment of neutrophils and macrophages, increasing the number of CD4+CD25+Foxp3+Tregs. Our findings support a critical role for CD4+CD25+Foxp3+Tregs in regulating from ALI pathophysiology, and a potential therapeutic role for the inhibition of Th17 cells in ALI treatment. These findings provide a rationale for treating patients with ALI by modulating CD4+CD25+Foxp3+Tregs and Th17 cells.