title: IL-17A and Multiple Sclerosis: Signaling Pathways, Producing Cells and Target Cells in the Central Nervous System.
abstract: Multiple sclerosis (MS) is an immune mediated demyelinating disease of the central nervous system (CNS). The importance of immune cells to MS pathology is supported by clinical data linking the depletion of T and B cells, or the prevention of their migration into the brain with significant reduction in relapses and development of new lesions. In vitro studies, preclinical animal models and encouraging data with the anti-IL-17A antibody secukinumab in a small proof of concept study in man, indicate that IL-17A, a key interleukin associated with many inflammatory and autoimmune diseases, may be involved in MS. Not only cells involved in adaptive immune responses such as Th17 cells and cytotoxic T cells, or innate immune responses such as mucosa-associated invariant T (MAIT) cells and γδT cells, but also CNS resident cells such as astrocytes and oligodendrocytes might contribute to the local production of IL-17A. IL-17A synergizes with other proinflammatory cytokines, by inducing the release of additional cytokines, mediators of tissue damage and chemokines, that recruit new inflammatory cells. IL-17A adversely affects the functions of microglia, astrocytes, oligodendrocytes, neurons, neural precursor cells and endothelial cells. Blockade of IL-17A might be beneficial to MS patients not only by inhibiting inflammation and tissue destruction, but also by enhancing repair processes.
authors.forename: Frank
authors.initials: F
authors.lastname: Kolbinger
authors.forename: Christine
authors.initials: C
authors.lastname: Huppertz
authors.forename: Anis
authors.initials: A
authors.lastname: Mir
authors.affiliation: Novartis Institutes for Biomedical Research, WSJ 386.11.48.38, 4002, Basel, Switzerland.
authors.forename: Franco Di
authors.initials: FD
authors.lastname: Padova
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009457:Neuroglia / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17