title: IL-27 and IL-27-producing CD4+ T cells in human tuberculous pleural effusion.
abstract: The objective of the present study was to figure out whether human IL-27-producing CD4(+) T cells represent a distinct T cell subset in tuberculosis pleural effusion (TPE). Distribution, phenotypic features of IL-27-producing CD4(+) T cells in TPE were determined. The required transcription factors and signal transductions for IL-27-producing CD4(+) T cell differentiation were explored. The immune regulation of IL-27 on pleural mesothelial cells was observed. We have determined the presence of a subset of human Th cells that infiltrated into tuberculous pleural effusion, which was characterized by the secretion of IL-27, and somehow IFN-γ, but not of IL-4, IL-9, IL-17, or IL-22. These IL-27-producing CD4(+) T cells were effector memory cells and exhibited a transcription profile clearly separated from those of Th2, Th17, Th9, and Th22 cells. The in vitro experiments showed that IL-1β, IL-2 and IL-12, or their various combinations could promote IL-27(+)CD4(+) T cell differentiation from naive CD4(+) T cells by means of phosphorylation of STAT3, STAT4, or/and STAT5. Transcription factors c-Fos and T-bet were required for IL-27(+)CD4(+) T cell differentiation. By activating STAT3 signaling, IL-27 not only restored a clear epithelial phenotype of pleural mesothelial cells, but also further reversed IFN-γ-induced epithelial-mesenchymal transition of pleural mesothelial cells. These data suggested that human IL-27(+)CD4(+) T cells might represent a distinct human T cell subset with unique expression profiles of transcription factors and proinflammatory cytokines, and these IL-27(+)CD4(+) T cells may play important roles in tuberculosis immunity by affecting pleural mesothelial cells.
authors.forename: Huan
authors.initials: H
authors.lastname: Xia
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Ye
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: You
authors.forename: Ai
authors.initials: A
authors.lastname: Cui
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Wang
authors.forename: Kan
authors.initials: K
authors.lastname: Zhai
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Jin
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Tong
authors.forename: Huan-Zhong
authors.initials: HZ
authors.lastname: Shi
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D064094:Interleukin-27 / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000276:immunology* / Q000382:microbiology; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology; D050791:STAT Transcription Factors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014396:Tuberculosis, Pleural / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D064094:Interleukin-27; D016760:Proto-Oncogene Proteins c-fos; D050791:STAT Transcription Factors; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma