title: Interferon-γ orchestrates the number and function of Th17 cells in experimental autoimmune encephalomyelitis.
abstract: Th17 cells are suggested to be pathogenic in mediating experimental autoimmune encephalomyelitis (EAE), but their relation to interferon (IFN)-γ-producing Th1 cells in vivo is not well understood. We studied the numbers and functions of Th17 cells in CREAE in Biozzi ABH mice, both in peripheral lymphoid organs and in the central nervous system. Th1 and Th17 cells alternated in secondary lymphoid organs and infiltrated into the central nervous system during chronic relapsing experimental autoimmune encephalomyelitis (CREAE). In the absence of IFN-γ the numbers and secretion of Th17 cells was enhanced, whereas exogenous administration of IFN-γ decreased the Th17 cells. In mice with intact IFN-γ genes, in vivo neutralization of interleukin (IL)-17 protected against EAE development by enhancing the number of IFN-γ-producing cells. IFN-γ knockout mice were partially protected by anti-IL-17 antibodies by decreasing cell numbers and production of IL-17. Our findings suggest that, whereas IFN-γ as such is not necessary for EAE development in the mouse, the lack of suppression of Th17 cells by IFN-γ enhances the susceptibility to develop EAE. IFN-γ thus orchestrates the number and function of Th17 cells.
authors.affiliation: Laboratory of Immunobiology, Faculty of Medicine, Rega Institute, University of Leuven, Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Berghmans
authors.forename: Amber
authors.initials: A
authors.lastname: Nuyts
authors.forename: Catherine
authors.initials: C
authors.lastname: Uyttenhove
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Snick
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Hubertine
authors.initials: H
authors.lastname: Heremans
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; D020381:Interleukin-17; D007371:Interferon-gamma