| First Author | Sosa RA | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 36 | Pages | E5038-47 |
| PubMed ID | 26305941 | Mgi Jnum | J:226814 |
| Mgi Id | MGI:5698598 | Doi | 10.1073/pnas.1505955112 |
| Citation | Sosa RA, et al. (2015) IFN-gamma ameliorates autoimmune encephalomyelitis by limiting myelin lipid peroxidation. Proc Natl Acad Sci U S A 112(36):E5038-47 |
| abstractText | Evidence has suggested both a pathogenic and a protective role for the proinflammatory cytokine IFN-gamma in experimental autoimmune encephalomyelitis (EAE). However, the mechanisms underlying the protective role of IFN-gamma in EAE have not been fully resolved, particularly in the context of CNS antigen-presenting cells (APCs). In this study we examined the role of IFN-gamma in myelin antigen uptake by CNS APCs during EAE. We found that myelin antigen colocalization with APCs was decreased substantially and that EAE was significantly more severe and showed a chronic-progressive course in IFN-gamma knockout (IFN-gamma-/-) or IFN-gamma receptor knockout (IFN-gammaR-/-) mice as compared with WT animals. IFN-gamma was a critical regulator of phagocytic/activating receptors on CNS APCs. Importantly, "free" myelin debris and lipid peroxidation activity at CNS lesions was increased in mice lacking IFN-gamma signaling. Treatment with N-acetyl-l-cysteine, a potent antioxidant, abolished lipid peroxidation activity and ameliorated EAE in IFN-gamma-signaling-deficient mice. Taken together the data suggest a protective role for IFN-gamma in EAE by regulating the removal of myelin debris by CNS APCs and thereby limiting the substrate available for the generation of neurotoxic lipid peroxidation products. |
