%0 Journal Article
%T IFN-¦Ã protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils
%A Carine Savarin
%A Stephen A Stohlman
%A David R Hinton
%A Richard M Ransohoff
%A Daniel J Cua
%A Cornelia C Bergmann
%J Journal of Neuroinflammation
%D 2012
%I BioMed Central
%R 10.1186/1742-2094-9-104
%X Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-¦Ã and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT) or IFN-¦Ã deficient (GKO) memory CD4+ T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade.Transfer of GKO memory CD4+ T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4+ T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4+ T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4+ T cells provided a model to directly assess their contribution(s) to disease. Recipients of WT CD4+ T cells depleted of IFN-¦Ã did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4+ T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4+ T cells prolonged survival in an IFN-¦Ã dependent manner, although IL-17 transcription was not reduced.These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-¦Ã-deprived environment, independent of extensive neutrophil accumulation or GM-CSF upregulation. The results also suggest that IFN-¦Ã overrides the detrimental IL-17 effector responses via a mechanism downstream of transcriptional regulation.
%K Central nervous system
%K Encephalomyelitis
%K CD4+ T cells
%K IFN-¦Ã
%K IL-17
%K Neutrophils
%K Neurotropic coronavirus
%U http://www.jneuroinflammation.com/content/9/1/104/abstract