title: Interferon regulatory factor 3 controls interleukin-17 expression in CD8 T lymphocytes.
abstract: IFN regulatory factor (IRF) 3 plays a key role in innate responses against viruses. Herein we assessed its contribution to T-cell activation. We observed that poly(I:C)-induced IRF3 activation in CD8 T cells represses IL-17 expression in a type I IFN-independent fashion. Even in the absence of poly(I:C), polyclonally activated naïve IRF3(-/-) CD8 T cells expressed high levels of IL-17 and IL-23R in comparison with wild-type cells. Furthermore, IRF3(-/-) OT1 cells adoptively transferred into wild-type hosts also produced higher IL-17 levels upon immunization than their wild-type counterparts. This phenotype could be reversed by ectopic expression of IRF3, confirming that this effect is intrinsic to T cells. We show that IRF3 directly interacts with RORγt in the cytoplasm through its IRF interaction domain and limits its ability to bind and transactivate the IL-17 promoter. These observations uncover an unexpected role of IRF3 in the control of CD8 T-cell polarization.
authors.affiliation: Institute for Medical Immunology, Walloon Excellence in Life sciences and BIOtechnology, Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.
authors.forename: Laure
authors.initials: L
authors.lastname: Ysebrant de Lendonck
authors.forename: Sandrine
authors.initials: S
authors.lastname: Tonon
authors.forename: Muriel
authors.initials: M
authors.lastname: Nguyen
authors.forename: Patricia
authors.initials: P
authors.lastname: Vandevenne
authors.forename: Iain
authors.initials: I
authors.lastname: Welsby
authors.forename: Valerie
authors.initials: V
authors.lastname: Martinet
authors.forename: Céline
authors.initials: C
authors.lastname: Molle
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Charbonnier
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D008156:Luciferases; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050838:Interferon Regulatory Factor-3; D020381:Interleukin-17; D008156:Luciferases
keywords: Tc17; Th17; cytokine; enhancer; transcription factor
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