Project A04

The role of cAMP in regulatory T cell homeostasis and function

Background

Treg cells have high levels of cAMP, which is known to suppress the inflammatory activity of effector T cells and dendritic cells (DCs) via cell-contact-dependent mechanisms. In effector T cells, cAMP is a potent negative regulator of T cell receptor-mediated activation and inhibits the expression of pro-inflammatory cytokines.

We hypothesize that Treg cell cAMP levels influence their gene expression profile through multiple intracellular pathways and result in the modulation of Treg cells and tolerogenic DCs activities in physiological and pathological contexts.

Strategy

We aim to dissect the influence of cAMP levels on the Treg cell suppressive capacity in vitro and in vivo. We will explore the intracellular pathways downstream of cAMP accumulation in Treg cells and their mediators. Through genetic manipulation of specific cell lines or the use of genetic mouse models, the potential mediators of cAMP signaling will be identified and their involvement in different T-cell driven autoimmune diseases will be investigated.