A role for IL-27 in limiting T regulatory cell populations

J Immunol. 2011 Jul 1;187(1):266-73. doi: 10.4049/jimmunol.1004182. Epub 2011 May 27.

Abstract

IL-27 is a cytokine that regulates Th function during autoimmune and pathogen-induced immune responses. Although previous studies have shown that regulatory T cells (Tregs) express the IL-27R, and that IL-27 inhibits forkhead box P3 upregulation in vitro, little is known about how IL-27 influences Tregs in vivo. The studies presented in this article show that mice that overexpress IL-27 had decreased Treg frequencies and developed spontaneous inflammation. Although IL-27 did not cause mature Tregs to downregulate forkhead box P3, transgenic overexpression in vivo limited the size of a differentiating Treg population in a bone marrow chimera model, which correlated with reduced production of IL-2, a vital cytokine for Treg maintenance. These data identify an indirect role for IL-27 in shaping the Treg pool.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation / immunology
  • Bone Marrow Transplantation / pathology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Female
  • Growth Inhibitors / biosynthesis
  • Growth Inhibitors / genetics
  • Growth Inhibitors / physiology*
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-2 / antagonists & inhibitors
  • Interleukin-2 / biosynthesis
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Interleukins / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Protein Subunits / biosynthesis
  • Protein Subunits / genetics
  • Protein Subunits / physiology*
  • Radiation Chimera / immunology
  • Receptors, Cytokine / biosynthesis
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / physiology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Ebi3 protein, mouse
  • Growth Inhibitors
  • Il27 protein, mouse
  • Interleukin-2
  • Interleukins
  • Minor Histocompatibility Antigens
  • Protein Subunits
  • Receptors, Cytokine