title: Expression of Th17-related genes in PHA/IL-2-activated human T cells by Fas signaling via caspase-1- and Stat3-dependent pathway.
abstract: T helper 17 (Th17) cells, which produce interleukin 17 (IL-17), are involved in the pathogenesis of autoimmune diseases and inflammatory conditions. Th17 cells have been detected in many Fas ligand-positive tumors. This study investigates the expression of Th17-related genes in PHA/IL-2-activated human T cells upon Fas ligation. Activated T cells transiently express RORγt, IL-17A, and IL-17F. A subsequent Fas receptor stimulation or contact with FasL-expressing glioma cells significantly prolongs the induction of RORγt and Th17-related cytokines. Treatments with inhibitors of caspase-1 and Stat3 reduce the Fas-signal-associated induction of RORγt, IL-17A, and IL-17F, as well as the phosphorylation of Stat3. Although the ligation of Fas results in caspase-8 cleavage and ERK1/2 phosphorylation, inhibitors for caspase-8 and MEK have no effect on the expressions of RORγt, IL-17A, and IL-17F. The results suggest that the Fas signal favors the Th17-phenotypic features of human T cells through the caspase-1/Stat3 signaling pathway.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chung-Chen
authors.initials: CC
authors.lastname: Su
authors.forename: Huan-Ching
authors.initials: HC
authors.lastname: Lin
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Lin
authors.forename: Yan-Shen
authors.initials: YS
authors.lastname: Shan
authors.forename: Bei-Chang
authors.initials: BC
authors.lastname: Yang
mesh_terms: D015153:Blotting, Western; D020170:Caspase 1 / Q000276:immunology* / Q000378:metabolism; D053181:Caspase 8 / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology* / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D020381:Interleukin-17; D007376:Interleukin-2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010835:Phytohemagglutinins; D050796:STAT3 Transcription Factor; D019014:fas Receptor; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053181:Caspase 8; D020170:Caspase 1