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IL-12 signals through a heterodimeric receptor (IL-12R\u03b21\/IL-12R\u03b22), whose \u03b22-chain is up-regulated on activated, autoreactive Th1 cells. Contrary to the expectation that the absence of IL-12R\u03b22 would protect from EAE, we found that IL-12R\u03b22-deficient mice developed earlier and more severe disease, with extensive demyelination and CNS inflammation. The inflammatory cells were mainly comprised of CD4+ T cells, monocyte\/macrophages, and dendritic cells. Compared to wild-type mice, IL-12R\u03b22-deficient mice exhibited significantly increased autoantigen-induced proliferative response and increased production of TNF-\u03b1, GM-CSF, IL-17, IL-18\/IL-18R\u03b1, and NO. In addition, we found significantly increased levels of IL-23p19 mRNA expression in spleen cells from immunized IL-12R\u03b22\u2212\/\u2212 mice compared with wild-type mice. These findings indicate that IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the CNS, and that, in the absence of IL-12R\u03b22, increased IL-23 and other inflammatory molecules may be responsible for increased severity of EAE.<\/jats:p>","DOI":"10.4049\/jimmunol.170.4.2153","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T19:49:07Z","timestamp":1398109747000},"page":"2153-2160","source":"Crossref","is-referenced-by-count":246,"title":["Induction of Experimental Autoimmune Encephalomyelitis in IL-12 Receptor-\u03b22-Deficient Mice: IL-12 Responsiveness Is Not Required in the Pathogenesis of Inflammatory Demyelination in the Central Nervous System"],"prefix":"10.1093","volume":"170","author":[{"given":"Guang-Xian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Gran","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Siglienti","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"Kamoun","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdolmohamad","family":"Rostami","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,2,15]]},"reference":[{"key":"2026020210093579100_R1","first-page":"83","volume-title":"Adv. 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