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...
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| 格式: | Article |
| 語言: | English |
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Elsevier
2016-07-01
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| 叢編: | Cell Reports |
| 主題: | |
| 在線閱讀: | http://www.sciencedirect.com/science/article/pii/S221112471630701X |
| _version_ | 1828383066713751552 |
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| author | Gerd Meyer zu Horste Chuan Wu Chao Wang Le Cong Mathias Pawlak Youjin Lee Wassim Elyaman Sheng Xiao Aviv Regev Vijay K. Kuchroo |
| author_facet | Gerd Meyer zu Horste Chuan Wu Chao Wang Le Cong Mathias Pawlak Youjin Lee Wassim Elyaman Sheng Xiao Aviv Regev Vijay K. Kuchroo |
| author_sort | Gerd Meyer zu Horste |
| collection | DOAJ |
| 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 | 2024-12-10T04:43:19Z |
| format | Article |
| id | doaj.art-ad750fdbe8294565aafe901b7d5389df |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T04:43:19Z |
| publishDate | 2016-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ad750fdbe8294565aafe901b7d5389df2022-12-22T02:01:50ZengElsevierCell Reports2211-12472016-07-0116239240410.1016/j.celrep.2016.05.088RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor ExpressionGerd Meyer zu Horste0Chuan Wu1Chao Wang2Le Cong3Mathias Pawlak4Youjin Lee5Wassim Elyaman6Sheng Xiao7Aviv Regev8Vijay K. Kuchroo9Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02215, USAEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02215, USAEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02215, USAThe Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USAEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02215, USAEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02215, USAAnn Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02215, USAEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02215, USAThe Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USAEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02215, USAInterleukin-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.http://www.sciencedirect.com/science/article/pii/S221112471630701XTh17 cellspathogenicityIL-23RRBPJNotch |
| spellingShingle | Gerd Meyer zu Horste Chuan Wu Chao Wang Le Cong Mathias Pawlak Youjin Lee Wassim Elyaman Sheng Xiao Aviv Regev Vijay K. Kuchroo RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression Cell Reports Th17 cells pathogenicity IL-23R RBPJ Notch |
| 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 |
| topic | Th17 cells pathogenicity IL-23R RBPJ Notch |
| url | http://www.sciencedirect.com/science/article/pii/S221112471630701X |
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