dc.contributor.author | Meyer zu Horste, Gerd | |
dc.contributor.author | Wu, Chuan | |
dc.contributor.author | Wang, Chao | |
dc.contributor.author | Cong, Le | |
dc.contributor.author | Pawlak, Mathias | |
dc.contributor.author | Lee, Youjin | |
dc.contributor.author | Elyaman, Wassim | |
dc.contributor.author | Xiao, Sheng | |
dc.contributor.author | Regev, Aviv | |
dc.contributor.author | Kuchroo, Vijay K. | |
dc.date.accessioned | 2017-04-18T20:30:56Z | |
dc.date.available | 2017-04-18T20:30:56Z | |
dc.date.issued | 2016-06 | |
dc.date.submitted | 2016-01 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/108233 | |
dc.description.abstract | Interleukin-17 (IL-17)-producing helper T cells (Th17 cells) play an important role in autoimmune diseases. However, not all Th17 cells induce tissue inflammation or autoimmunity. Th17 cells require IL-23 receptor (IL-23R) signaling to become pathogenic. The transcriptional mechanisms controlling the pathogenicity of Th17 cells and IL-23R expression are unknown. Here, we demonstrate that the canonical Notch signaling mediator RBPJ is a key driver of IL-23R expression. In the absence of RBPJ, Th17 cells fail to upregulate IL-23R, lack stability, and do not induce autoimmune tissue inflammation in vivo, whereas overexpression of IL-23R rescues this defect and promotes pathogenicity of RBPJ-deficient Th17 cells. RBPJ binds and trans-activates the Il23r promoter and induces IL-23R expression and represses anti-inflammatory IL-10 production in Th17 cells. We thus find that Notch signaling influences the development of pathogenic and non-pathogenic Th17 cells by reciprocally regulating IL-23R and IL-10 expression. | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.celrep.2016.05.088 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | Elsevier | en_US |
dc.title | RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Meyer zu Horste, Gerd; et al. "RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression" Cell Reports, 16, no. 2 (2016 July): 392-404. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.mitauthor | Regev, Aviv | |
dc.relation.journal | Cell Reports | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Meyer zu Horste, Gerd; Wu, Chuan; Wang, Chao; Cong, Le; Pawlak, Mathias; Lee, Youjin; Elyaman, Wassim; Xiao, Sheng; Regev, Aviv; Kuchroo, Vijay K. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8567-2049 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |