ID: 161: An unknown T cell-associated protective role of IFN-I in the development of experimental autoimmune encephalomyelitis (EAE)

Although interferon beta (IFN β ) is used as first-line treatment for multiple sclerosis (MS), the cell type-specific activity of type I IFNs in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), as well as the role of endogenous type I IFNs versus exogenous IFN β remain obscure. The objective of this study, is to elucidate the in vivo immunomodulatory role of IFN-I signaling in T cells during EAE using a novel transgenic mouse, which expresses functional type I IFN receptor (IFNAR1) exclusively on T lymphocytes (IFNAR1Texcl). When MOG-EAE was induced to the IFNAR1Texcl mice a milder disease development was observed. Histopathological analysis of the spinal cord of the mice showed reduced T cell infiltration, demyelination and axonal damage. Noteworthy, exogenous IFN- β almost abrogated EAE in IFNAR1Texcl mice as compared to untreated littermates. In vivo analysis demonstrated that during the priming phase of EAE, endogenous IFNAR signaling in T cells led to impaired Th17 responses, with a reduced fraction of CCR6+ CD4+ T cells in the periphery. At the acute phase, an increased proportion of IL-10- and IFN- γ producing CD4+ T cells was detected in the periphery of IFNAR1Texcl mice, accompanied by up-regulation of the IFN- γ induced gene, Irgm1, in peripheral T cells. Together these results reveal a hitherto unknown splenic T lymphocyte-associated protective role of IFN-I in EAE. Investigation of the underlying mechanisms of IFN-I activity during the priming phase of EAE in the IFNAR1Texcl is needed. These information may provide valuable clues for designing novel therapeutic strategies for MS.