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PMID: 22981537 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Immunity ·Vol. 37 ·No. 3 ·2012-09-21 ·Pages 511-23

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

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.

MeSH Terms
Animals Cell Differentiation/drug effects,immunology Cells, Cultured Female Flow Cytometry Forkhead Transcription Factors/genetics,immunology,metabolism Gene Expression Profiling Interferon-gamma/genetics,immunology,pharmacology Interleukin-17/genetics,immunology,pharmacology Male Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Knockout Mice, Transgenic Oligonucleotide Array Sequence Analysis Receptors, CXCR3/genetics,immunology,metabolism STAT1 Transcription Factor/genetics,immunology,metabolism Salmonella Infections, Animal/immunology,microbiology,pathology Salmonella typhimurium/immunology T-Box Domain Proteins/genetics,immunology,metabolism T-Lymphocytes, Regulatory/drug effects,immunology,metabolism Toxoplasma/immunology Toxoplasmosis, Animal/immunology,parasitology,pathology
Chemicals
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
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Hall Aisling O'Hara
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Beiting Daniel P
Tato Cristina
John Beena
Oldenhove Guillaume
Lombana Claudia Gonzalez
Pritchard Gretchen Harms
Silver Jonathan S
Bouladoux Nicolas
Stumhofer Jason S
Harris Tajie H
Grainger John
Wojno Elia D Tait
Wagage Sagie
Roos David S
Scott Philip
Turka Laurence A
Cherry Sara
Reiner Steven L
Cua Daniel
Belkaid Yasmine
Elloso M Merle
Hunter Christopher A
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2012.06.014
Published
2012-09-21
Epub
2012-00-13
Pages
511-23
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3477519
Subset
IM
Grants
NIAID NIH HHS · AI084882 · United States
NIAID NIH HHS · R01 AI042334 · United States
NIAID NIH HHS · R37-AI28724 · United States
NIAID NIH HHS · T32 AI055428 · United States
NIAID NIH HHS · T32 AI007532 · United States
NIAID NIH HHS · AI 071302 · United States
NIAID NIH HHS · R37 AI028724 · United States
NIAID NIH HHS · AI055428 · United States
NIAID NIH HHS · R21-AI090234-01 · United States
NIAID NIH HHS · P01 AI043620 · United States
NIAID NIH HHS · R21 AI090234 · United States
NIAID NIH HHS · R01 AI061699 · United States
NIAID NIH HHS · T32 AI055400 · United States
Databases
GEO
GSE38686
Corrections
CommentIn
PMID: 22999950
External Links
PubMed source DOI: 10.1016/j.immuni.2012.06.014 PMC Full Text View journal details
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