IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients

Immunol Lett. 2010 Jan 4;127(2):150-6. doi: 10.1016/j.imlet.2009.10.006. Epub 2009 Nov 4.

Abstract

Interleukin-17-producing CD4(+) T cells (Th17 cells) are the dominant pathogenic cellular component in autoimmune inflammatory diseases, including autoimmune arthritis. IL-10 promotes the generation of Foxp3(+) regulatory T cells via the IL-10 receptor signal. The objective of this study was to examine whether IL-10, which acts as an anti-inflammatory cytokine, has a suppressive effect on the activation of human Th17 cells. Expression of IL-17 and IL-10 was examined immunohistochemically in tissue obtained from rheumatoid arthritis patients. Human peripheral blood CD4(+) T cells were isolated and cultured under various stimulatory conditions. Th17 cells and regulatory T (Treg) cells were detected by flow cytometry. The gene expression of related cytokines and transcription factors were assessed by ELISA and RT-PCR. IL-17 was overexpressed in rheumatoid arthritis patients. IL-10 treatment significantly decreased the numbers of IL-17-producing and RORc-expressing cells among human CD4(+) T cells that had been activated in vitro by Th17-differentiating conditions in autoimmune arthritis patients. IL-10 induced Foxp3(+) regulatory T cells in the human CD4(+) T cell population. Our results demonstrate that IL-17 is overexpressed in autoimmune disease patients and that IL-10 suppresses IL-17 expression. IL-10 may be useful in the treatment of autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • CD4 Antigens / biosynthesis
  • Cells, Cultured
  • Forkhead Transcription Factors / biosynthesis
  • Gene Expression Regulation
  • Humans
  • Immunosuppression Therapy
  • Interleukin-10 / pharmacology
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Lymphocyte Activation / drug effects
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / biosynthesis*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Recombinant Proteins / pharmacology
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Recombinant Proteins
  • Interleukin-10