RBPJ Controls Development of Pathogenic Th17 Cells by Regulating IL-23 Receptor Expression
2016
Summary
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
pathogenicityof Th17 cells and IL-23R expression are unknown. Here, we demonstrate that the canonical Notch signaling mediator
RBPJis 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
pathogenicityof
RBPJ-deficient Th17 cells.
RBPJbinds 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
pathogenicand non-
pathogenicTh17 cells by reciprocally regulating IL-23R and IL-10 expression.
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