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Myelin-reactive CD4 T cells play critical roles in the formation of acute inflammatory lesions and disease progression in MS and experimental autoimmune encephalomyelitis (EAE), a well-defined mouse model for MS. Current MS therapies are only partially effective, making it necessary to develop more effective therapies that specifically target pathogenic myelin-specific CD4 T cells for MS treatment. While suppressing T-bet, the key transcription factor in T helper type 1 (Th1) cells, has been demonstrated to be beneficial in prevention and treatment of EAE, the therapeutic potential of retinoic acid-related orphan receptor gamma t (ROR)\u03b3t, the key transcription factor for Th17 cells, has not been well-characterized. In this study, we characterized the correlation between ROR\u03b3t expression and other factors affecting T cell encephalitogenicity and evaluated the therapeutic potential of targeting ROR\u03b3t by siRNA inhibition of ROR\u03b3t. Our data showed that ROR\u03b3t expression correlates with interleukin (IL)-17 production, but not with the encephalitogenicity of myelin-specific CD4 T cells. IL-23, a cytokine that enhances encephalitogenicity, does not enhance ROR\u03b3t expression significantly. Additionally, granulocyte\u2013macrophage colony-stimulating factor (GM-CSF) levels, which correlate with the encephalitogenicity of different myelin-specific CD4 T cell populations, do not correlate with ROR\u03b3t. More importantly, inhibiting ROR\u03b3t expression in myelin-specific CD4 T cells with an siRNA does not reduce disease severity significantly in adoptively transferred EAE. Thus, ROR\u03b3t is unlikely to be a more effective therapeutic target for ameliorating pathogenicity of encephalitogenic CD4 T cells.<\/jats:p>","DOI":"10.1111\/cei.12441","type":"journal-article","created":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T03:17:21Z","timestamp":1408591041000},"page":"108-118","source":"Crossref","is-referenced-by-count":28,"title":["Impact of suppressing retinoic acid-related orphan receptor gamma<i>t<\/i>(ROR)\u03b3t in ameliorating central nervous system autoimmunity"],"prefix":"10.1093","volume":"179","author":[{"given":"Y","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R C","family":"Winger","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P W","family":"Lee","sequence":"additional","affiliation":[{"name":"Molecular Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P K","family":"Nuro-Gyina","sequence":"additional","affiliation":[{"name":"Postbacculaureate Research Education Program, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Minc","sequence":"additional","affiliation":[{"name":"Summer Research Opportunities Program, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Rieser","sequence":"additional","affiliation":[{"name":"Neuroscience program, College of Arts and Sciences, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M K","family":"Racke","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA"},{"name":"Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A E","family":"Lovett-Racke","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA"},{"name":"Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,11,26]]},"reference":[{"key":"2021122010114521300_cei12441-bib-0001","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1056\/NEJMra052130","article-title":"Multiple sclerosis \u2013 the plaque and its pathogenesis","volume":"354","author":"Frohman","year":"2006","journal-title":"N Engl J Med"},{"key":"2021122010114521300_cei12441-bib-0002","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/ni1507","article-title":"Multiple sclerosis: a complicated picture of autoimmunity","volume":"8","author":"McFarland","year":"2007","journal-title":"Nat Immunol"},{"key":"2021122010114521300_cei12441-bib-0003","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.bbadis.2010.05.012","article-title":"Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis?","volume":"1812","author":"Lovett-Racke","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"2021122010114521300_cei12441-bib-0004","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","article-title":"Two types of murine helper T cell clone. 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