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Among the risk alleles that have repeatedly been identified by genome-wide association studies, three are located near the Casitas B-lineage lymphoma proto-oncogene b gene (CBLB). The CBLB protein (CBL-B) is a key regulator of peripheral immune tolerance by limiting T cell activation and expansion and hence T cell\u2013mediated autoimmunity through its ubiquitin E3-ligase activity. In this study, we show that CBL-B expression is reduced in CD4+ T cells from relapsing-remitting MS (RR-MS) patients during relapse. The MS risk-related single nucleotide polymorphism of CBLB rs12487066 is associated with diminished CBL-B expression levels and alters the effects of type I IFNs on human CD4+ T cell proliferation. Mechanistically, the CBLB rs12487066 risk allele mediates increased binding of the transcription factor C\/EBP\u03b2 and reduced CBL-B expression in human CD4+ T cells. Our data suggest a role of the CBLB rs12487066 variant in the interactions of a genetic risk factor and IFN function during viral infections in MS.<\/jats:p>","DOI":"10.4049\/jimmunol.1303077","type":"journal-article","created":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T03:29:33Z","timestamp":1411788573000},"page":"4439-4447","source":"Crossref","is-referenced-by-count":26,"title":["A Multiple Sclerosis\u2013Associated Variant of CBLB Links Genetic Risk with Type I IFN Function"],"prefix":"10.1093","volume":"193","author":[{"given":"Klarissa Hanja","family":"St\u00fcrner","sequence":"first","affiliation":[{"name":"Institute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf , 20251 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Borgmeyer","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf , 20251 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schulze","sequence":"additional","affiliation":[{"name":"Systems Biology, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf , 20251 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Pless","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Molecular Biology and Applied Ecology, ScreeningPort , 22525 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Martin","sequence":"additional","affiliation":[{"name":"Institute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf , 20251 Hamburg ,","place":["Germany"]},{"name":"Neuroimmunology and MS Research Section, Department of Neurology, University Hospital Z\u00fcrich , CH-8091 Z\u00fcrich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,11,1]]},"reference":[{"key":"2025030707414001900_r1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S1474-4422(10)70094-6","article-title":"Multiple sclerosis: risk factors, prodromes, and potential causal pathways","volume":"9","author":"Ramagopalan","year":"2010","journal-title":"Lancet Neurol."},{"key":"2025030707414001900_r2","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev.immunol.23.021704.115707","article-title":"Immunology of multiple sclerosis","volume":"23","author":"Sospedra","year":"2005","journal-title":"Annu. 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