Project B10 - Regulation of a human Th17 cell polarized tissue resident memory fate in the skin

So far, the diversity of human T helper cell fates has almost exclusively been studied in the recirculating blood compartment, leaving tissue resident human T cells (TRM) largely unexplored. In this project we will investigate skin T cells from patients after allogeneic stem cell transplantation (> 6 months – 5 years). The existence of Th17 cells within the resident host T cell population will be determined based on their gene expression profile, and molecular and transcriptional checkpoints that differentially regulate tissue adaptation and residency within Th17 cells will be compared to other T helper cell subsets to obtain insights into the trajectory of their developmental pathways. As T cell functions are tailored towards their cognate antigens, we plan to assess microbial antigen specificities of tissue resident Th17 and investigate the differential response of tissue resident versus recirculating Th17 cells towards immunosuppressive therapies. Taken together, our project will assess the existence and maintenance of human skin resident Th17 cells as well as their molecular and transcriptional checkpoints, which will provide novel therapeutic targets for the treatment of Th17 cell-mediated chronic inflammatory diseases such as psoriasis.