Expression of Th17-related genes in PHA/IL-2-activated human T cells by Fas signaling via caspase-1- and Stat3-dependent pathway

Cell Immunol. 2013 Feb;281(2):101-10. doi: 10.1016/j.cellimm.2013.03.002. Epub 2013 Mar 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Caspase 1 / immunology*
  • Caspase 1 / metabolism
  • Caspase 8 / immunology
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Fas Ligand Protein / immunology
  • Fas Ligand Protein / metabolism
  • Gene Expression / immunology
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology
  • Jurkat Cells
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mitogen-Activated Protein Kinase 1 / immunology
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / immunology
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Models, Immunological
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Phosphorylation / drug effects
  • Phosphorylation / immunology
  • Phytohemagglutinins / immunology
  • Phytohemagglutinins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / immunology*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • fas Receptor / immunology*
  • fas Receptor / metabolism

Substances

  • Fas Ligand Protein
  • Interleukin-17
  • Interleukin-2
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Phytohemagglutinins
  • STAT3 Transcription Factor
  • fas Receptor
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Caspase 8
  • Caspase 1