title: IL-12/IFN-gamma/NO axis plays critical role in development of Th1-mediated experimental autoimmune encephalomyelitis.
abstract: The importance of the IL-12/IFN-gamma/nitric oxide (NO) axis in the pathogenesis of autoimmune diseases remains controversial. In parallel experiments, we explored the role of the IL-12/IFN-gamma/NO axis in the development of MOG 35-55-induced experimental autoimmune encephalomyelitis (EAE) in mice lacking IL-12, IFN-gamma receptor (IFN-gammaR) and inducible nitric oxide synthase (NOS2), respectively. In comparison with wide-type control mice, IL-12-/-, IFN-gammaR-/- and NOS2-/- mice displayed more severe clinical signs of EAE both in remission and at subsequent relapse. Given the relatively low IFN-gamma production in IL-12-/- mice and the lack of IFN-gamma/IFN-gammaR signaling pathway in IFN-gammaR-/- mice, IL-12-/-, IFN-gammaR-/- and NOS2-/- mice with EAE exhibited low NO production. This correlated negatively with MOG 35-55-induced T cell proliferation. Both ED1-positive macrophages and CD4-positive T cells were increased in spinal cords from IL-12-/-, IFN-gammaR-/- and NOS2-/- compared to control mice. In vitro experiments demonstrate that spleen mononuclear cells from IL-12-/-, IFN-gammaR-/- and NOS2-/-mice with EAE present stronger migration capacity when compared to control mice. These results reveal that the IL-12/IFN-gamma/NO axis plays a critical role in the development of MOG 35-55-induced EAE, possibly over failing NO production.
authors: Institute of Neurology, Huashan Hospital, Shanghai Medical College, and Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 12 Middle Wulumuqi Road, 200040 Shanghai, China.bgxiao@shmu.edu.cn
authors: Bao-Guo
authors: BG
authors: Xiao
authors: Cun-Gen
authors: CG
authors: Ma
authors: Ling-Yun
authors: LY
authors: Xu
authors: Hans
authors: H
authors: Link
authors: Chuan-Zhen
authors: CZ
authors: Lu
mesh_terms: D000818:Animals; D002633:Chemotaxis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D006023:Glycoproteins / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D009569:Nitric Oxide / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013116:Spinal Cord / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma