Modulation of Regulatory T cell Plasticity and Functions through the T cell receptor signaling molecules Themis1 and Vav1 – MoRegPaF

Regulatory T cells (Treg) are of paramount importance for establishing self-tolerance and their manipulation harbors enormous therapeutic potential in a wide spectrum of diseases, ranging from autoimmunity to chronic inflammatory and infectious disorders. Our recent studies revealed that Themis1 and Vav1, two TCR signaling molecules, cooperate in the same signalosome to control Treg functions and plasticity. We propose to decipher the molecular mechanisms involved using a combination of unique mouse models, phosphoproteomics-based signaling studies and genome-wide transcriptomic and epigenetic approaches. This work shall ultimately identify novel molecules that could be manipulated to influence the stability and the suppressive function of Treg. In the long-term, these molecules might contribute to the development of new pharmaceutical compounds to quantitatively or qualitatively modulate Treg functions in immune-mediated disorders.