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IL-17A 产生的 γδT 细胞抑制恶性胸腔积液的形成。

IL-17A-Producing γδT Cells Inhibit the Formation of Malignant Pleural Effusions.

机构信息

1Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.

2Center of Medical Research and.

出版信息

Am J Respir Cell Mol Biol. 2019 Aug;61(2):174-184. doi: 10.1165/rcmb.2018-0201OC.

Abstract

γδT cells are an important source of IL-17A and play an anti- or protumor role depending on the surrounding microenvironment. The precise role of γδT cells in the development of malignant pleural effusions (MPE) remains unknown. Using flow cytometry, we analyzed the distribution and differentiation of γδT cells in wild-type (WT) and mice. We carefully elucidated the influence of γδT cells on the formation of MPE by depleting γδT cells from WT, , and mice. The distribution of γδT17 cells in human MPE and peripheral blood was also determined. Our data showed that both γδT cells and IL-17A-producing γδT (γδT17) cells accumulated in murine MPE, and IL-10 deficiency enhanced their accumulation. γδT cells were the main source of IL-17A in MPE for both WT and mice. IL-10 inhibited the chemotactic response of γδT cells to MPE and the proliferation of these cells. IL-10 suppressed γδT cell secretion of IL-17A via RORγt. The ablation of γδT cells accelerated MPE accumulation in both WT and mice, but it did not influence MPE accumulation in mice. Patients with higher frequencies of γδT17 cells had significantly longer survival times than patients with lower frequencies of γδT17 cells. Taken together, our data demonstrate that γδT17 cells play an inhibitory role in the progression of MPE, and the accumulation of γδT17 cells in MPE is suppressed by IL-10.

摘要

γδT 细胞是 IL-17A 的重要来源,其在肿瘤微环境中的作用具有双重性,既可以发挥抗肿瘤作用,也可以促进肿瘤生长。γδT 细胞在恶性胸腔积液(MPE)发生发展中的作用机制尚不清楚。本研究通过流式细胞术分析野生型(WT)和 小鼠γδT 细胞的分布和分化,并用流式细胞术分选的方法从 WT、和 小鼠中清除 γδT 细胞,探讨γδT 细胞在 MPE 形成中的作用。同时检测人 MPE 及外周血中 γδT17 细胞的分布情况。结果显示,γδT 细胞及其分泌的 IL-17A(γδT17)在 MPE 中明显积聚,IL-10 缺陷促进了其积聚。在 WT 和 小鼠中,IL-10 均主要通过抑制 RORγt 抑制 γδT 细胞向 MPE 的趋化反应和增殖,从而抑制 γδT 细胞分泌 IL-17A。清除 γδT 细胞可加速 WT 和 小鼠 MPE 的积聚,但对 小鼠 MPE 无明显影响。γδT17 细胞频率较高的患者生存时间明显长于 γδT17 细胞频率较低的患者。综上所述,γδT17 细胞在 MPE 的进展中发挥抑制作用,IL-10 抑制 MPE 中 γδT17 细胞的积聚。

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