biostudies-literatureUnknown7(10)Li LUnderstanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-β and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-βRII Il2ra^-/- (abbreviated as Il2ra^-/-Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. Il2ra^-/-Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3-4 weeks of age. Importantly, peripheral Treg cells from Il2ra^-/-Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro suppCell death & diseasee2439https://www.ebi.ac.uk/biostudies/studies/S-EPMC5134002biostudies-literatureBlock of both TGF-β and IL-2 signaling impedes Neurophilin-1⁺ regulatory T cell and follicular regulatory T cell development.PMC5134002Ma HDYao YXie YQGershwin MYang YQYang SHYin XYLian ZXLi LWang YHfalseBlock of both TGF-β and IL-2 signaling impedes Neurophilin-1⁺ regulatory T cell and follicular regulatory T cell development.Understanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-β and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-βRII Il2ra^-/- (abbreviated as Il2ra^-/-Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. Il2ra^-/-Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3-4 weeks of age. Importantly, peripheral Treg cells from Il2ra^-/-Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro supp2016-01-01T00:00:00Z2016 Oct2025-04-03T23:23:38.561Z2019-03-27T02:30:34ZS-EPMC51340022778751410.1038/cddis.2016.348