title: Unlike αβ T cells, γδ T cells, LTi cells and NKT cells do not require IRF4 for the production of IL-17A and IL-22.
abstract: Apart from conventional CD4(+) Th17 cells, the cytokines IL-17A and IL-22 can also be produced by γδ T cells, NK cells and lymphoid tissue inducer (LTi) cells. Th17 cells develop from precursor cells after T-cell receptor stimulation in the presence of TGF-β, IL-6 and IL-23. In contrast, a subset of γδ T cells ("γδT17") is committed for fast IL-17 production already in the thymus; however, γδ T cells can also produce IL-17 after prolonged in vitro stimulation via their γδ T-cell receptor plus IL-23. Here, we show that γδ T-, LTi- and NKT cells differ extensively from Th17 cells in their signalling requirements for the generation of IL-17A and IL-22. While production of these cytokines by Th17 cells totally depends on the transcription factor interferon regulatory factor 4 (IRF4), IRF4 is irrelevant in the other cell types. As for γδ T cells, this finding pertains to both thymic commitment and prolonged in vitro culture. Furthermore, IL-17A-producing γδ T cells accumulate in the central nervous system of IRF4 deficient (Irf4(-/-)) mice during experimental autoimmune encephalomyelitis. IL-17A-producing WT and Irf4(-/-) γδ T cells equally express CCR6 and lack CD27. The underlying IRF4-independent pathway partially involves STAT3 during in vitro stimulation.
authors.affiliation: Institut für medizinische Mikrobiologie und Krankenhaushygiene, Philipps Universität Marburg, Marburg, Germany.
authors.forename: Hartmann
authors.initials: H
authors.lastname: Raifer
authors.forename: Azita J
authors.initials: AJ
authors.lastname: Mahiny
authors.forename: Nadine
authors.initials: N
authors.lastname: Bollig
authors.forename: Franziska
authors.initials: F
authors.lastname: Petermann
authors.forename: Anne
authors.initials: A
authors.lastname: Hellhund
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kellner
authors.forename: Anna
authors.initials: A
authors.lastname: Guralnik
authors.forename: Katharina
authors.initials: K
authors.lastname: Reinhard
authors.forename: Evita
authors.initials: E
authors.lastname: Bothur
authors.forename: Magdalena
authors.initials: M
authors.lastname: Huber
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauer
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
authors.forename: Elina A
authors.initials: EA
authors.lastname: Kiss
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Ganal
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
authors.forename: Thomas
authors.initials: T
authors.lastname: Korn
authors.forename: Michael
authors.initials: M
authors.lastname: Lohoff
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054399:Receptors, CCR6 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000097043:Interleukin-22; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054399:Receptors, CCR6; D050796:STAT3 Transcription Factor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000097043:Interleukin-22; D000099218:Interferon Regulatory Factor-4; C498126:CCR6 protein, mouse; C098680:Il17a protein, mouse; C494087:Stat3 protein, mouse