| First Author | Naves R | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 6 | Pages | 2967-77 |
| PubMed ID | 23960239 | Mgi Jnum | J:205866 |
| Mgi Id | MGI:5546551 | Doi | 10.4049/jimmunol.1300419 |
| Citation | Naves R, et al. (2013) The interdependent, overlapping, and differential roles of type I and II IFNs in the pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 191(6):2967-77 |
| abstractText | Type I IFNs (IFN-alpha and IFN-beta) and type II IFN (IFN-gamma) 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-gamma signaling is ablated, type I IFNs drive inflammation, resulting in exacerbated EAE. IFN-gamma has a disease stage-specific opposing function in EAE. Treatment of mice with IFN-gamma during the initiation phase of EAE leads to enhanced severity of disease. In contrast, IFN-gamma treatment during the effector phase attenuated disease. This immunosuppressive activity of IFN-gamma required functional type I IFN signaling. In IFN-alpha/beta receptor-deficient mice, IFN-gamma 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. |
