[en] Recent evidence suggests a pivotal role of the proinflammatory cytokine interleukin - 17A (IL-17) in demyelinating autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS). Nevertheless, it remains unclear if this cytokine exerts direct effects on CNS resident cells during MS or modulates the function of infiltrating immune cells towards a more detrimental phenotype. Here, we investigated the effects of locally produced IL-17 during experimental demyelination of the CNS using the cuprizone (CPZ) model in mice with (GF/IL17) or without transgenic production of IL-17 by astrocytes in the CNS. During early demyelination, GF/IL17 mice demonstrated enhanced activity and decreased anxiety-related behavior in the elevated plus maze suggesting a more severe disease course. Furthermore, in GF/IL17 mice, toxic demyelination was accelerated and synthesis of myelin proteins was reduced. Early demyelination was accompanied by an increased ratio of infiltrating granulocytes in GF/ILl17 mice. The presence of IL-17 during CPZ treatment increased the accumulation of activated microglia and sustained microglial proliferation during myelin loss. Taken together, our results argue for a detrimental role of IL-17 during demyelinating diseases.
Disciplines :
Neurology
Author, co-author :
Zimmermann, Julian ; Department of Neurology, University of Bonn, Sigmund-Freud-Str 25, 53127, Bonn, Germany. julian.zimmermann@ukb.uni-bonn.de
Emrich, Michael; Department of Neurology, University of Bonn, Sigmund-Freud-Str 25, 53127, Bonn, Germany
Krauthausen, Marius; Department of Neurology, University of Bonn, Sigmund-Freud-Str 25, 53127, Bonn, Germany
Saxe, Simon; Department of Neurology, University of Bonn, Sigmund-Freud-Str 25, 53127, Bonn, Germany
Nitsch, Louisa; Department of Neurology, University of Bonn, Sigmund-Freud-Str 25, 53127, Bonn, Germany
HENEKA, Michael ; Clinical Neurosciences, Department of Neurology, University of Bonn, Bonn, Germany
Campbell, Iain L; School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia
Müller, Marcus; Department of Neurology, University of Bonn, Sigmund-Freud-Str 25, 53127, Bonn, Germany
External co-authors :
yes
Language :
English
Title :
IL-17A Promotes Granulocyte Infiltration, Myelin Loss, Microglia Activation, and Behavioral Deficits During Cuprizone-Induced Demyelination.
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