Regulatory T (Treg) cells are the primary mediators of peripheral tolerance and their alteration is one of the major causes of autoimmune disorders. Bcl11b is an essential transcriptional regulator for T lineage differentiation and maintenance of T cell identity, as well as for innate lymphoid identity and function. Here we provide evidence that early and efficient removal of Bcl11b in Treg cells causes early death of mice despite the fact that Treg cells are formed in normal numbers. However, Bcl11b-/- Treg cells are unable to block Tcell induced colitis due to major reduction in genes controlling the conversion of extracellular ATP, released in inflammatory conditions, into suppressive pericellular adenosine, as well as IL10. We propose experiments to investigate the regulation by Bcl11b of Treg cell genetic program at steady state and in inflammatory conditions, including exploring genomic regions regulated by Bcl11b, with main emphasis on suppression function. These studies have high relevance for autoimmune diseases.
T regulatory (Treg) cells are the primary mediators of peripheral tolerance and their alteration is one of the major causes of autoimmune disorders. This grant application aims to decipher mechanisms implicated in function of these cells, which is critical for development of therapeutic strategies for autoimmune disease treatement.