BioProject

Notch receptors direct the differentiation of T helper (Th) cell subsets, but their influence on regulatory T (TR) cell responses is obscure. More...

Notch receptors direct the differentiation of T helper (Th) cell subsets, but their influence on regulatory T (TR) cell responses is obscure. Interruption of Notch signaling in TR cells resulted in a super-regulatory phenotype, with suppression of TR cell Th1 programming and apoptosis as well as Th1 cell responses in systemic inflammation. In contrast, gain of function Notch1 signaling in TR cells resulted in lymphoproliferation, dysregulated Th1 responses and autoimmunity. To determine mechanisms by which Notch signaling may alter TR cell function, we compared the transcriptional profiles of splenic TR cells of Foxp3EGFPCre mice with those of Foxp3EGFPCreR26N1c/N1c (gain of function Notch signaling), Foxp3EGFPCreRBPJ∆/∆ (loss of function canonical Notch signaling), and Foxp3EGFPCreR26N1c/N1cRBPJ∆/∆ mice (gain of function/canonical loss of function Notch signaling). Overall design: Regulatory T cells are isolated from the spleen of 6 weeks old males, based on the expression of CD3, TCRbeta, CD4 and GFP (Foxp3), after Red blood cell lysis by ACK and gate on lineage negative (CD8, B220, CD11b, CD11c, Gr1) cells. To reduce variability and increase cell number, cells from multiple mice were pooled for sorting and at least three replicates were generated for all groups. RNA from 4.0-5.0x104 cells was amplified, labeled and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays Less...