title: IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice.
abstract: The clear association of Th17 cells with autoimmune pathogenicity implicates Th17 cytokines as critical mediators of chronic autoimmune diseases such as EAE. To study the impact of IL-17A on CNS inflammation, we generated transgenic mice in which high levels of expression of IL-17A could be initiated after Cre-mediated recombination. Although ubiquitous overexpression of IL-17A led to skin inflammation and granulocytosis, T cell-specific IL-17A overexpression did not have a perceptible impact on the development and health of the mice. In the context of EAE, neither the T cell-driven overexpression of IL-17A nor its complete loss had a major impact on the development of clinical disease. Since IL-17F may be able to compensate for the loss of IL-17A, we also generated IL-17F-deficient mice. This strain was fully susceptible to EAE and displayed unaltered emergence and expansion of autoreactive T cells during disease. To eliminate potential compensatory effects of either cytokine, we treated IL-17F-deficient mice with antagonistic monoclonal antibodies specific for IL-17A and found again only a minimal beneficial impact on disease development. We conclude therefore that both IL-17A and IL-17F, while prominently expressed by an encephalitogenic T cell population, may only marginally contribute to the development of autoimmune CNS disease.
authors.affiliation: Neuroimmunology Division, Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Haak
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Croxford
authors.forename: Katharina
authors.initials: K
authors.lastname: Kreymborg
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pouly
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006098:Granulocytes / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D006023:Glycoproteins; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)