The role of c-Rel and IkBNS in the development of regulatory T cells

Regulatory T-cells are key players for the maintenance of immune homeostasis. Moreover, they establish a threshold for the activation of effector T cells and regulate the duration and strength of an immune response. Recent studies demonstrated, that the transcription factor NF-kB and proteins regulating its activity are crucial for the development of regulatory T cells. Especially the NF-kB-subunit c Rel appears to be important, since c-Rel-deficient mice show a systemic reduction of regulatory T cells by 50%. The activity of NF-kB is regulated by so called inhibitors of NF-kB (IkB) proteins and IkBNS belongs to the group of unusual IkB proteins, that are inducible and obligatory nuclear. Remarkably, it has the potential to modulate transcription in both, an inducing and repressive manner. Our analyses revealed a 50% reduction of regulatory T cells in IkBNS-deficient mice. The phenotypical similarities of IkBNS- and c-Rel-deficient mice suggest a functional or molecular interaction of both proteins. The aim of this project is a detailed analysis of how IkBNS and c-Rel regulate Foxp3 induction and the development of regulatory T cells in vivo. To this end, we will investigate a potential functional interaction between IkBNS and c-Rel by analyzing mice, which are deficient for both genes. Moreover, we are planning to unravel the molecular mechanisms, by which c-Rel and IkBNS govern regulatory T cell development

Beteiligte Gruppen

Geldgeber / Förderer

DFG - Deutsche Forschungsgemeinschaft

DruckenPer Mail versendenTeilen