title: IFNγ inhibits Th17 differentiation and function via Tbet-dependent and Tbet-independent mechanisms.
abstract: The transcription factor Tbet is critical for the differentiation of Th1 CD4 T cells and is associated with the induction of multiple autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate that Tbet suppresses IL-17A and Th17 differentiation both in vitro and in vivo in a cell-intrinsic manner, and that in fact, Tbet is not necessary for EAE induction. Moreover, we find that IFNγ inhibits the production of IL-17A and IL-17F in a STAT1-dependent, Tbet-independent manner. These findings illustrate multiple mechanisms utilized by developing Th1 cells to silence the Th17 program.
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, United States.
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Yeh
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, United States.
authors.forename: Ian L
authors.initials: IL
authors.lastname: McWilliams
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, United States. Electronic address: lharring@uab.edu.
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Harrington
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects; D002490:Central Nervous System / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D020381:Interleukin-17 / Q000378:metabolism / Q000494:pharmacology*; D007378:Interleukins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000187:drug effects*; D000098546:Interleukin-21
chemical_list: D015704:CD4 Antigens; D018398:Homeodomain Proteins; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539901:Rorc protein, mouse; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D000098546:Interleukin-21
keywords: CD4 T cell; Experimental autoimmune encephalomyelitis; IFNγ; IL-17A; Tbet