Regulation of Th17 responses by the protein kinase Tec kinase

T helper cells play a crucial role during adaptive immune responses. Among those subsets, Th17 cells were shown to be essential for the clearance of extracellular bacteria and fungi. Th17 cells are also important modulators of autoimmune and allergic responses. Recently, Th17 cells were subdivided in pathogenic and non pathogenic subgroups, dependent on the cytokine milieu which led to their differentiation and it was even proposed that Th17 do not represent an end-stage helper subset, but rather a transient population that arises in response to inflammation and can convert to other T helper lineages. Since Th17 cells are linked with immune-related diseases, it is important to understand in detail how their differentiation and function is regulated. In a previous study we could show that the protein tyrosine kinase Tec regulates Th17 cell differentiation in vivo, in part due to T cell-intrinsic mechanisms. In this application, we propose to elucidate the mechanisms and signaling pathways that are regulated by Tec in more detail. Moreover, to study the role of Tec in Th17-dependent immune responses, we are proposing to investigate the contribution of Tec to Th17 differentiation processes using IL17F, IL17A and RORt EFYP/EGFP reporter mice that allow us to track Th17 cells in vivo. We expect to our proposed study will provide mechanistic insights into how Tec regulates Th17 differentiation/function at a cellular and molecular level.