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The Interdependent, Overlapping, and Differential Roles of Type I and II IFNs in the Pathogenesis of Experimental Autoimmune Encephalomyelitis.
- Source :
-
Journal of Immunology . 9/15/2013, Vol. 191 Issue 6, p2967-2977. 11p. - Publication Year :
- 2013
-
Abstract
- Type I IFNs (IFN-α and IFN-β) and type II IFN (IFN-γ) mediate both regulation and inflammation in multiple sclerosis, neuromyelitis optica, and in experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanism for these Janus-like activities of type I and II IFNs in neuroinflammation remains unclear. Although endogenous type I IFN signaling provides a protective response in neuroinflammation, we find that when IFN-γ signaling is ablated, type I IFNs drive inflammation, resulting in exacerbated EAE. IFN-γ has a disease stage-specific opposing function in EAE. Treatment of mice with IFN-γ during the initiation phase of EAE leads to enhanced severity of disease. In contrast, IFN-γ treatment during the effector phase attenuated disease. This immunosuppressive activity of IFN-γ required functional type I IFN signaling. In IFN-α/β receptor-deficient mice, IFN-γ treatment during effector phase of EAE exacerbated disease. Using an adoptive transfer EAE model, we found that T cell-intrinsic type I and II IFN signals are simultaneously required to establish chronic EAE by encephalitogenic Th1 cells. However, in Th17 cells loss of either IFN signals leads to the development of a severe chronic disease. The data imply that type I and II IFN signals have independent but nonredundant roles in restraining encephalitogenic Th17 cells in vivo. Collectively, our data show that type I and II IFNs function in an integrated manner to regulate pathogenesis in EAE. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 191
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 103555552
- Full Text :
- https://doi.org/10.4049/jimmunol.1300419