The interdependent, overlapping, and differential roles of type i and II IFNs in the pathogenesis of experimental autoimmune encephalomyelitis

Academic Article


  • 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-g 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-g treatment during the effector phase attenuated disease. This immunosuppressive activity of IFN-g 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. Copyright © 2013 by The American Association of Immunologists, Inc.
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    Digital Object Identifier (doi)

    Author List

  • Naves R; Singh SP; Cashman KS; Rowse AL; Axtell RC; Steinman L; Mountz JD; Steele C; De Sarno P; Raman C
  • Start Page

  • 2967
  • End Page

  • 2977
  • Volume

  • 191
  • Issue

  • 6