Abstract
Notch receptors direct the differentiation of T helper (TH) cell subsets, but their influence on regulatory T (Treg) cell responses is obscure. We here report that lineage-specific deletion of components of the Notch pathway enhanced Treg cell-mediated suppression of TH1 responses, and protected against their TH1 skewing and apoptosis. Expression in Treg cells of gain of function transgene encoding Notch1 intracellular domain resulted in lymphoproliferation, exacerbated TH1 responses and autoimmunity. Cell-intrinsic canonical Notch signaling impaired Treg cell fitness, promoted the acquisition by Treg cells of a TH1 cell-like phenotype, whereas Rictor-dependent non-canonical Notch signaling activated the AKT-Foxo1 axis and impaired Foxp3 epigenetic stability. These findings establish a critical role for Notch signaling in controlling peripheral Treg cell functions.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
