title: IFN-γ limits Th9-mediated autoimmune inflammation through dendritic cell modulation of IL-27.
abstract: IL-9-producing Th9 cells have been associated with autoimmune diseases, such as experimental autoimmune encephalitis. However, the factors that negatively regulate Th9 cells during autoimmune inflammation are unclear. In this article, we show that IFN-γ inhibits Th9 differentiation both in vitro and in vivo. This suppressive activity was dependent on the transcription factor STAT-1. In addition to its direct inhibitory effect on Th9 differentiation, IFN-γ suppressed Th9 cells through the induction of IL-27 from dendritic cells. In vitro, treatment of naive CD4(+) T cells with IL-27 suppressed the development of Th9 cells, which was partially dependent on the transcription factors STAT-1 and T-bet. Moreover, IL-27 treatment completely abrogated the encephalitogenicity of Th9 cells in the experimental autoimmune encephalomyelitis model. Thus, our results identify a previously unknown mechanism by which IFN-γ limits Th9-mediated autoimmune inflammation through dendritic cell modulation of IL-27.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Gopal
authors.initials: G
authors.lastname: Murugaiyan
authors.forename: Vanessa
authors.initials: V
authors.lastname: Beynon
authors.forename: Andre
authors.initials: A
authors.lastname: Pires Da Cunha
authors.forename: Nicole
authors.initials: N
authors.lastname: Joller
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D016906:Interleukin-9 / Q000096:biosynthesis / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: C486767:Il27 protein, mouse; D020381:Interleukin-17; D016906:Interleukin-9; D007378:Interleukins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma