IFN-? deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response.
Autor(es): Zhang Hong-Liang; Azimullah Sheikh; Zheng Xiang-Yu; Wang Xiao-Ke; Amir Naheed; Mensah-Brown Eric P; Al Shamsi Mariam; Shahin Allen; Press Rayomand; Zhu Jie; Adem Abdu
Resumo: Previous studies have shown that interferon-gamma (IFN-?) is a proinflammatory cytokine that contributes to the pathogenesis of Guillain-Barré syndrome and its animal model, experimental autoimmune neuritis (EAN). Treatments with anti-IFN-? antibodies improve clinical outcome in GBS patients and EAN animals and administration of IFN-? markedly worsens EAN. Paradoxically, the mice deficient in IFN-? remain susceptible to experimental autoimmune encephalomyelitis, an analogous disease in the central nervous system. These observations raise a question whether IFN-? might be protective in autoimmune demyelinating diseases. To clarify the role of IFN-? in the pathogenesis of autoimmune demyelinating diseases, we used P0 protein peptide 180-199 to induce EAN in IFN-? knockout (KO) mice. After the acute phase of EAN, the clinical signs of IFN-? KO mice were significantly more severe than those of wild type (WT) controls. After antigenic stimulation, the proliferation of splenic mononuclear cells was significantly higher in IFN-? KO than in WT mice with EAN. At the peak of EAN, the proportion of interleukin (IL)-17A expressing cells in cauda equina (CE) infiltrating cells, and the levels of IL-17A in sera were elevated in IFN-? KO mice when compared with their WT counterparts. The proportions of major histocompatibility complex (MHC) II, macrosialin, and IL-12/IL-23p40 expressing cells, relative to total CE infiltrating cells were correspondingly higher in IFN-? KO than in WT mice with EAN. However, IFN-? deficiency reduced the production of NO by cultured macrophages in response to proinflammatory stimuli and induced a systemic Th2-oriented immune response. In conclusion, IFN-? deficiency exacerbates EAN via upregulating Th17 cells despite a mitigated systemic Th1 immune response.
Imprenta: Journal of Neuroimmunology, v. 246, n. 1-2, p. 18-26, 2012
Identificador do objeto digital: 10.1016/j.jneuroim.2012.02.011
Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Cytokines ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Immunology
Data de publicação: 2012
