Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism

作     者：Yong Lu Hua Lin Kan Zhai Xiaojuan Wang Qiong Zhou Huanzhong Shi 

作者机构：Department of Respiratory and Critical Care Medicine Beijing Chaoyang Hospital Capital Medical University Department of Respiratory and Critical Care Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2016年第59卷第12期

页      面：1297-1304页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (91442109, 31470883, 81270149, 81272591) the National Basic Research Program of China (2012CB518706) 

主　　题：malignant pleural effusion interleukin 17 Th9 cells 

摘      要：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 the in vivo differentiation 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 from 1L-17-/- mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription faclLors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleurai tumors, and thus accelerated the death of mice bearing MPE. The in vivo administration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exoge- nous IL-9 improved the survival of IL-17-/- mice. Our data provide the first definitive evidence that IL-17 promotes the differ- entiation 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.