删除干扰素gamma对室降验性自身免疫性神经炎的作用.docVIP

IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice via upregulating Th17 cells despite a mitigated systemic Th1 immune response Hong-Liang Zhang1, Xiang-Yu Zheng1, Azimullan Sheikh2, Xiao-Ke Wang1,3, Naheed Amir2, Rayomand Press4, Abdu Adem2, Jie Zhu1,5,* 1Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden 2Department of Pharmacology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates 3Department of Neurosurgery, Second Hospital of Jilin University, Changchun, China 4Division of Neurology, Department of Clinical Neuroscience, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden 5Department of Neurology, First Hospital of Jilin University, Changchun, China *Corresponding author: Dr Jie Zhu, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Karolinska University Hospital Huddinge, Novum, plan 5, SE141 86, Stockholm, Sweden (Tel. +46 8 Fax. +46 8 E-mail: Jie.Zhu@ki.se). Abstract Previous studies have shown that interferon (IFN)-g is a proinflammatory cytokine that contributes to the pathogenesis of Guillain-Barré syndrome (GBS), an inflammatory demyelinating disease of the peripheral nervous system (PNS) in humans, and its animal model, experimental autoimmune neuritis (EAN). Treatments with anti-IFN-g antibodies can improve clinical outcome in GBS patients and EAN animals. Administration of IFN-g markedly worsened EAN. Paradoxically, the mice deficient in IFN-γ remain susceptible to experimental autoimmune encephalomyelitis, an analogous disease in the central nervous system. These observations raise a question whether IFN-γ might be protective in autoimmune demyelinating diseases. To clarify the role of IFN-g in the pathogenesis of autoimmune demyelinating disease, we used P0 protein peptide 180-199 to induce EAN in IFN-g knockout (KO) mice. After the acute phase