RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression
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 th...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/108233 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826191581998219264 |
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| author | Meyer zu Horste, Gerd Wu, Chuan Wang, Chao Cong, Le Pawlak, Mathias Lee, Youjin Elyaman, Wassim Xiao, Sheng Regev, Aviv Kuchroo, Vijay K. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Meyer zu Horste, Gerd Wu, Chuan Wang, Chao Cong, Le Pawlak, Mathias Lee, Youjin Elyaman, Wassim Xiao, Sheng Regev, Aviv Kuchroo, Vijay K. |
| author_sort | Meyer zu Horste, Gerd |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:58:09Z |
| format | Article |
| id | mit-1721.1/108233 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:58:09Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1082332022-09-30T12:29:48Z RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression Meyer zu Horste, Gerd Wu, Chuan Wang, Chao Cong, Le Pawlak, Mathias Lee, Youjin Elyaman, Wassim Xiao, Sheng Regev, Aviv Kuchroo, Vijay K. Massachusetts Institute of Technology. Department of Biology Regev, Aviv 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. 2017-04-18T20:30:56Z 2017-04-18T20:30:56Z 2016-06 2016-01 Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/108233 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. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1016/j.celrep.2016.05.088 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Meyer zu Horste, Gerd Wu, Chuan Wang, Chao Cong, Le Pawlak, Mathias Lee, Youjin Elyaman, Wassim Xiao, Sheng Regev, Aviv Kuchroo, Vijay K. RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression |
| title | RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression |
| title_full | RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression |
| title_fullStr | RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression |
| title_full_unstemmed | RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression |
| title_short | RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression |
| title_sort | rbpj controls development of pathogenic th17 cells by regulating il 23 receptor expression |
| url | http://hdl.handle.net/1721.1/108233 https://orcid.org/0000-0001-8567-2049 |
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