IL-12p35-Deficient Mice Are Susceptible to Experimental Autoimmune Encephalomyelitis: Evidence for Redundancy in the IL-12 System in the Induction of Central Nervous System Autoimmune Demyelination

• DOI: 10.4049/jimmunol.169.12.7104
• Publication Date: 2014-04-21T00:33:07Z
• Authors: Bruno Gran; Guang-Xian Zhang; Shuo Yu; Jifen Li; Xiao-Han Chen; Elvira S Ventura; Malek Kamoun; Abdolmohamad Rostami
• Keywords: Myelin oligodendrocyte glycoprotein; Encephalomyelitis

Abstract Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis and is considered CD4+, Th1 cell-mediated disease. IL-12 heterodimeric cytokine, composed of p40 p35 subunit, which thought to play an important role in the development cells can exacerbate EAE. We induced EAE with myelin oligodendrocyte glycoprotein (MOG) peptide 35–55 (MOG35–55) C57BL/6 mice found that while IL-12p40-deficient (−/−) are resistant EAE, IL-12p35−/− susceptible. Typical spinal cord mononuclear cell infiltration demyelination were observed wild-type mice, whereas IL-12p40−/− had normal cords. A Th1-type response MOG35–55 was draining lymph node spleen mice. weaker MOG35–55-specific lower production IFN-γ. By contrast, Th2-type correlated disease resistance Production TNF-α by microglia, CNS-infiltrating macrophages, CD4+ T detected IL-12p35−/−, but not IL-12p40−/−, In addition, NO higher than These data demonstrate redundancy system induction suggest p40-related heterodimers, such recently cloned IL-23 (p40p19), may pathogenesis.