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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
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RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression
Gerd Meyer Zu Horste1, Chuan Wu1, Chao Wang1
1Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02215, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02215, USA.
Cell Reports
|June 28, 2016
Summary
Notch signaling mediator RBPJ controls pathogenic T helper 17 (Th17) cell development by regulating IL-23R expression. RBPJ is crucial for Th17 cell stability and pathogenicity in autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-17 (IL-17)-producing helper T (Th17) cells are implicated in autoimmune diseases.
- Not all Th17 cells are pathogenic; pathogenicity is linked to IL-23 receptor (IL-23R) signaling.
- The transcriptional regulation of Th17 cell pathogenicity and IL-23R expression remains unclear.
Purpose of the Study:
- To investigate the role of Notch signaling, specifically RBPJ, in regulating Th17 cell pathogenicity.
- To elucidate the mechanisms by which RBPJ controls IL-23R expression and Th17 cell function.
Main Methods:
- Investigated RBPJ's role in Th17 cell differentiation and function.
- Analyzed IL-23R and IL-10 expression in RBPJ-deficient Th17 cells.
- Examined the effect of RBPJ on the Il23r promoter activity.
- Assessed the impact of RBPJ on Th17 cell-induced autoimmune inflammation in vivo.
Main Results:
- RBPJ is essential for IL-23R expression in Th17 cells.
- RBPJ-deficient Th17 cells lack stability and fail to induce autoimmune inflammation.
- Overexpression of IL-23R can rescue the pathogenic defect in RBPJ-deficient Th17 cells.
- RBPJ directly binds and trans-activates the Il23r promoter, increasing IL-23R expression.
- RBPJ represses anti-inflammatory IL-10 production in Th17 cells.
Conclusions:
- Canonical Notch signaling mediator RBPJ is a key regulator of IL-23R expression in Th17 cells.
- RBPJ controls the balance between pathogenic and non-pathogenic Th17 cell development.
- RBPJ reciprocally regulates IL-23R and IL-10 expression, influencing Th17 cell-mediated autoimmunity.
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