Project B02

Impact of CCR4 ligands on tissue Treg cells in islet autoimmunity

Background

The chemokines CCL22 and CCL17 are important mediators of T cell trafficking with anti- or pro-inflammatory properties, respectively. Their receptor CCR4 is highly expressed on Treg cells and CCL22-CCR4 interaction induces dendritic cell (DC)-Treg cellular contacts leading to immune suppression.

We hypothesize that the chemokines CCL22 and CCL17 may impact the development of Type 1 Diabetes (T1D) by interfering with the function, induction and stability of Treg cells.

Strategy

We make use of gain- and loss-of-function mouse models for components of the CCR4-CCL22/CCL17 axis for in-depth analysis of Treg cell phenotypes. The impact of the chemokines’ action on islet autoimmunity is then studied using non-obese diabetic (NOD) mice and streptozotocin (STZ)-induced T1D.