RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression
Name
Horste-2016-RBPJ Controls Develo.pdf
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9.43 MB
Format
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Author(s)
Meyer zu Horste, Gerd
Wu, Chuan
Wang, Chao
Cong, Le
Pawlak, Mathias
Lee, Youjin
Elyaman, Wassim
Xiao, Sheng
Regev, Aviv
Kuchroo, Vijay K.
Date Issued
June 2016
Journal
Cell Reports
Publisher
Elsevier
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.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2016.05.088
