8^th European Immunology Conference

Biography

Biography: Ping Wang

Abstract

T cell mediated responses are controlled by checkpoints that limit over-activation of effector cells and excessive pathology. However, over control of the checkpoints will lead to weak immune responses. It is less known about the intrinsic mechanisms in effector T cells to regulate the balance of checkpoint molecules in response to different stimuli. Transcription factors early growth response gene (Egr) 2 and 3, induced in effector phenotype T cells by antigens, are intrinsic regulators served as checkpoint controllers to promote clonal expansion in adaptive immune responses, but inhibit inflammatory differentiation of effector T cells. Induction of Egr2 and 3 at early stage of anti-viral responses promote proliferation, but suppress differentiation of antigen specific T cells for optimal expansion with minimum inflammatory pathology. The expression of Egr2 and 3 are inhibited at late stage by inflammatory cytokines which is essential for activation of differentiation checkpoint of effector T cells. In homeostasis, Egr2 and 3 controls differentiation of effector phenotype T cells. CD2-specific deletion of Egr2 and 3 results in server autoimmune diseases. Egr2 and 3 regulate expression of proliferative regulators such as Myc, while inhibit inflammatory transcription factors such as T-bet and RORgt. Thus, temporal and spatial expression of Egr2 and 3, induced by antigen and inhibited by inflammatory cytokines, control checkpoints of clonal expansion and differentiation of effector T cells in both adaptive and homeostatic responses. This control is essential for both optimal adaptive immune responses and maintaining immune homeostasis.