Block of both TGF-β and IL-2 signaling impedes Neurophilin-1⁺ regulatory T cell and follicular regulatory T cell development.

ABSTRACT: 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 supp

SUBMITTER: Li L 

PROVIDER: S-EPMC5134002 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature