title: The cytokines interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology.
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.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Aisling O'Hara
authors.initials: AO
authors.lastname: Hall
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Beiting
authors.forename: Cristina
authors.initials: C
authors.lastname: Tato
authors.forename: Beena
authors.initials: B
authors.lastname: John
authors.forename: Guillaume
authors.initials: G
authors.lastname: Oldenhove
authors.forename: Claudia Gonzalez
authors.initials: CG
authors.lastname: Lombana
authors.forename: Gretchen Harms
authors.initials: GH
authors.lastname: Pritchard
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Silver
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.forename: Jason S
authors.initials: JS
authors.lastname: Stumhofer
authors.forename: Tajie H
authors.initials: TH
authors.lastname: Harris
authors.forename: John
authors.initials: J
authors.lastname: Grainger
authors.forename: Elia D Tait
authors.initials: ED
authors.lastname: Wojno
authors.forename: Sagie
authors.initials: S
authors.lastname: Wagage
authors.forename: David S
authors.initials: DS
authors.lastname: Roos
authors.forename: Philip
authors.initials: P
authors.lastname: Scott
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
authors.forename: Sara
authors.initials: S
authors.lastname: Cherry
authors.forename: Steven L
authors.initials: SL
authors.lastname: Reiner
authors.forename: Daniel
authors.initials: D
authors.lastname: Cua
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: M Merle
authors.initials: MM
authors.lastname: Elloso
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D000098815:T-bet Transcription Factor
chemical_list: C515188:Cxcr3 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D054367:Receptors, CXCR3; D050794:STAT1 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma