Project A07
Investigating Treg cell plasticity in mice and man
Background
Significant differences exist between human and mouse Treg cells. This is particularly exemplified in the expression specificity and stability of the key lineage transcription factor Foxp3. The NF-κB transcription factor c-Rel centrally controls Treg cell activation and immune-regulated functions in mice, while its role in human Treg cells remains largely unclear.
We hypothesize that understanding the context-dependent transcriptional networks in Treg cells will enable us to modulate distinct features to ultimately generate next-generation cell therapies for autoimmune and other diseases.
Strategy
We aim to compare central Treg cell identity and function programs between mice and men in normal physiology and autoimmunity. We furthermore elucidate the transcriptional networks regulated by Foxp3 and c-Rel in Treg cells in both species and screen for novel critical regulators in autoimmune contexts. We study how signaling induced by context-specific cytokine milieus affect Treg cell identity as well as plasticity and how we can functionally validate engineered Treg cells with distinct anti- or proinflammatory features.