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dc.contributor.authorKurdi, Ahmed T.en_US
dc.contributor.authorBassil, Ribalen_US
dc.contributor.authorOlah, Martaen_US
dc.contributor.authorWu, Chuanen_US
dc.contributor.authorXiao, Shengen_US
dc.contributor.authorTaga, Marikoen_US
dc.contributor.authorFrangieh, Michaelen_US
dc.contributor.authorButtrick, Thomasen_US
dc.contributor.authorOrent, Williamen_US
dc.contributor.authorBradshaw, Elizabeth M.en_US
dc.contributor.authorKhoury, Samia J.en_US
dc.contributor.authorElyaman, Wassimen_US
dc.date.accessioned2016-11-18T20:47:30Z
dc.date.issued2016en_US
dc.identifier.citationKurdi, A. T., R. Bassil, M. Olah, C. Wu, S. Xiao, M. Taga, M. Frangieh, et al. 2016. “Tiam1/Rac1 complex controls Il17a transcription and autoimmunity.” Nature Communications 7 (1): 13048. doi:10.1038/ncomms13048. http://dx.doi.org/10.1038/ncomms13048.en
dc.identifier.issn2041-1723en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29408341
dc.description.abstractRORγt is a master transcription factor of Th17 cells and considered as a promising drug target for the treatment of autoimmune diseases. Here, we show the guanine nucleotide exchange factor, Tiam1, and its cognate Rho-family G protein, Rac1, regulate interleukin (IL)17A transcription and autoimmunity. Whereas Tiam1 genetic deficiency weakens IL-17A expression partially and inhibits the development of experimental autoimmune encephalomyelitis (EAE), deletion of Rac1 in T cells exhibits more robust effects on Th17 cells and EAE. We demonstrate Tiam1 and Rac1 form a complex with RORγt in the nuclear compartment of Th17 cells, and together bind and activate the Il17 promoter. The clinical relevance of these findings is emphasized by pharmacological targeting of Rac1 that suppresses both murine and human Th17 cells as well as EAE. Thus, our findings highlight a regulatory pathway of Tiam1/Rac1 in Th17 cells and suggest that it may be a therapeutic target in multiple sclerosis.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/ncomms13048en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062600/pdf/en
dash.licenseLAAen_US
dc.titleTiam1/Rac1 complex controls Il17a transcription and autoimmunityen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature Communicationsen
dash.depositing.authorKurdi, Ahmed T.en_US
dc.date.available2016-11-18T20:47:30Z
dc.identifier.doi10.1038/ncomms13048*
dash.authorsorderedfalse
dash.contributor.affiliatedOrent, Will
dash.contributor.affiliatedTaga, Mariko
dash.contributor.affiliatedOlah, Marta
dash.contributor.affiliatedKurdi, Ahmed T.
dash.contributor.affiliatedWu, Chuan
dash.contributor.affiliatedElyaman, Wassim
dash.contributor.affiliatedBradshaw, Elizabeth M.
dash.contributor.affiliatedKhoury, Samia


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