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

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.

Pubmed ID: 22981537

Authors

  • Hall AO
  • Beiting DP
  • Tato C
  • John B
  • Oldenhove G
  • Lombana CG
  • Pritchard GH
  • Silver JS
  • Bouladoux N
  • Stumhofer JS
  • Harris TH
  • Grainger J
  • Wojno ED
  • Wagage S
  • Roos DS
  • Scott P
  • Turka LA
  • Cherry S
  • Reiner SL
  • Cua D
  • Belkaid Y
  • Elloso MM
  • Hunter CA

Journal

Immunity

Publication Data

September 21, 2012

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI 071302
  • Agency: NIAID NIH HHS, Id: AI055428
  • Agency: NIAID NIH HHS, Id: AI084882
  • Agency: NIAID NIH HHS, Id: P01 AI043620
  • Agency: NIAID NIH HHS, Id: R01 AI042334
  • Agency: NIAID NIH HHS, Id: R21-AI090234-01
  • Agency: NIAID NIH HHS, Id: R37-AI28724
  • Agency: NIAID NIH HHS, Id: T32 AI007532
  • Agency: NIAID NIH HHS, Id: T32 AI055400
  • Agency: NIAID NIH HHS, Id: T32 AI055428

Mesh Terms

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