The cytokines interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology

Immunity. 2012 Sep 21;37(3):511-23. doi: 10.1016/j.immuni.2012.06.014. Epub 2012 Sep 13.

Abstract

Interferon-γ (IFN-γ) promotes a population of T-bet(+) CXCR3(+) regulatory T (Treg) cells that limit T helper 1 (Th1) cell-mediated pathology. Our studies demonstrate that interleukin-27 (IL-27) also promoted expression of T-bet and CXCR3 in Treg cells. During infection with Toxoplasma gondii, a similar population emerged that limited T cell responses and was dependent on IFN-γ in the periphery but on IL-27 at mucosal sites. Transfer of Treg cells ameliorated the infection-induced pathology observed in Il27(-/-) mice, and this was dependent on their ability to produce IL-10. Microarray analysis revealed that Treg cells exposed to either IFN-γ or IL-27 have distinct transcriptional profiles. Thus, IFN-γ and IL-27 have different roles in Treg cell biology and IL-27 is a key cytokine that promotes the development of Treg cells specialized to control Th1 cell-mediated immunity at local sites of inflammation.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Profiling
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-17 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Receptors, CXCR3 / metabolism
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • STAT1 Transcription Factor / metabolism
  • Salmonella Infections, Animal / immunology*
  • Salmonella Infections, Animal / microbiology
  • Salmonella Infections, Animal / pathology
  • Salmonella typhimurium / immunology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Toxoplasma / immunology
  • Toxoplasmosis, Animal / immunology*
  • Toxoplasmosis, Animal / parasitology
  • Toxoplasmosis, Animal / pathology

Substances

  • Cxcr3 protein, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Receptors, CXCR3
  • STAT1 Transcription Factor
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interferon-gamma

Associated data

  • GEO/GSE38686