Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism.
Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism.
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Interleukin-17 通过 IL-9 依赖性机制抑制恶性胸腔积液的发展。
DOI：
10.1007/s11427-016-0097-y
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Shi Huanzhong
中科院分区：
文献类型：
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作者：
Lu Yong;Lin Hua;Zhai Kan;Wang Xiaojuan;Zhou Qiong;Shi Huanzhong
Th 17和Th 9细胞在恶性胸腔积液（MPE）中具有免疫调节功能。然而，IL-17是否能影响MPE中Th 9细胞的分化和功能尚不清楚。本研究的目的是探讨IL-17对MPE小鼠模型中Th 9细胞相对于Th 2细胞在体内分化的影响，并探讨IL-17是否通过IL-9 β依赖性机制抑制MPE的形成。IL-17-/-小鼠MPE中Th 9和Th 2细胞数较野生型小鼠减少。IL-17缺乏分别通过抑制转录因子IRF 4和加塔-3抑制Th 9和Th 2细胞分化。IL-17缺乏通过促进胸膜肿瘤的血管生成和增殖而促进MPE的形成，从而加速携带MPE的小鼠的死亡。抗IL-9中和mAb的体内给药加速WT小鼠的死亡;而外源性IL-9的给药改善了IL-17-/-小鼠的存活。我们的数据提供了IL-17促进MPE中Th 9和Th 2细胞分化的第一个明确证据。我们的研究结果还表明，IL-17抑制MPE的形成，并通过IL-9依赖性机制提高MPE小鼠的生存率。
Th17 and Th9 cells have been demonstrated to possess immune regulatory functions in malignant pleural effusion (MPE). However, whether IL-17 can affect differentiation and function of Th9 cells in MPE remains unknown. The objective of the present study was to explore the impact of IL-17 on thein vivodifferentiation of Th9 cells in relation to Th2 cells in a murine model of MPE, and to explore whether IL-17 inhibits MPE formation via IL-9‒dependent mechanism. It was found that Th9 and Th2 cells were decreased in MPE fromIL-17–/–mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription factors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleural tumors, and thus accelerated the death of mice bearing MPE. Thein vivoadministration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exogenous IL-9 improved the survival ofIL-17–/–mice. Our data provide the first definitive evidence that IL-17 promotes the differentiation of Th9 and Th2 cells in MPE. Our findings also demonstrate that IL-17 inhibits the formation of MPE and improves the survival of mice bearing MPE via an IL-9–dependent mechanism.