title: Immune Regulation of Toll-Like Receptor 2 Engagement on CD4+T Cells in Murine Models of Malignant Pleural Effusion.
abstract: Toll-like receptor (TLR) 2 has a well-known role in sensing multiple ligands that include microbial products, endotoxin, and some extracellular matrix molecules; however, its role in the development of malignant pleural effusion (MPE) remains unknown. We performed the present study to explore the impact of TLR2 signaling on the development of MPE and to define the underlying mechanisms by which TLR2 works. Development of MPE was compared between TLR2-/-and wild-type (WT) mice. The effect of TLR2 on differentiation of T helper type 17 (Th17), Th9, and Th2 cells in MPE was explored. The mechanisms of TLR2 on survival of mice bearing MPE were also investigated. MPE volume in TLR2-/-mice was lower than that in WT mice, and the survival of TLR2-/-mice bearing MPE was longer than that of WT mice. TLR2 deficiency increased, and TLR2 activation decreased, Th17 cells in MPE, whereas TLR2 signaling showed the contrary effects on Th2 cells. Th9 cells were increased in MPE of TLR2-/-mice but were not influenced by TLR2 signaling. Intraperitoneal injection of anti-IL-17 monoclonal antibody (mAb), anti-IL-9 mAb, or recombinant mouse IL-4 accelerated the death of TLR2-/-mice bearing MPE, and intraperitoneal injection anti-IL-17 mAb in TLR2-/-mice was associated with a significantly shorter survival time than in WT mice. We have demonstrated, for the first time, that TLR2 signaling promotes the development of MPE and accelerates the death of mice bearing MPE by directly suppressing Th17 cell differentiation and directly promoting Th2 cell differentiation, and also by indirectly suppressing Th9 cell differentiation via an IL-17-dependent mechanism.
authors: 1 Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Xiu-Zhi
authors: XZ
authors: Wu
authors: 2 Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.
authors: Qiong
authors: Q
authors: Zhou
authors: 2 Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.|3 Department of Respiratory and Critical Care Medicine, Hebei General Hospital, Shijiazhuang, China.
authors: Hua
authors: H
authors: Lin
authors: 1 Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Kan
authors: K
authors: Zhai
authors: 1 Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Xiao-Juan
authors: XJ
authors: Wang
authors: 2 Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.
authors: Wei-Bing
authors: WB
authors: Yang
authors: 1 Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Huan-Zhong
authors: HZ
authors: Shi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D016066:Pleural Effusion, Malignant / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D020381:Interleukin-17; D051195:Toll-Like Receptor 2
keywords: Th17 cells; Th2 cells; Th9 cells; Toll-like receptor 2; malignant pleural effusion