title: Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism.
abstract: 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 IL-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. The in vivo administration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exogenous IL-9 improved the survival of IL-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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Zhai
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. zhouqiongtj@126.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. shihuanzhong@sina.com.
authors.forename: Huanzhong
authors.initials: H
authors.lastname: Shi
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007274:Injections, Intraperitoneal; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D016066:Pleural Effusion, Malignant / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D049268:Positron-Emission Tomography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D000099218:Interferon Regulatory Factor-4
chemical_list: D057134:Antibodies, Neutralizing; D050990:GATA3 Transcription Factor; D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D016906:Interleukin-9; D000099218:Interferon Regulatory Factor-4; C494748:Gata3 protein, mouse
keywords: Th9 cells; interleukin 17; malignant pleural effusion