Co-receptors of CD8+ T cells in chronic skin inflammation

The immune system of our body has different functions. One of the most important tasks is the protection against invading pathogens without concurrent organ damage. Various immune cells are known to exhibit different functions. T cells are responsible together with antibody-producing B and plasma cells for the immune memory, which is essential to recognize pathogens after a first contact or after vaccination and rapidly confer protection. A certain population of T cells, so called cytotoxic T cells, is important for the defence against viruses, but can induce damage of organs in the context of auto-immune diseases. Various proteins on the surface of T cells, so called receptors, can regulate their function and their interactions with target cells that might be infected with pathogens or recognized by T cells in auto-immune processes. Although T cells play an important role in chronic inflammatory skin diseases, the role of individual receptors for their activation or inhibition is not well understood. The integrity of the skin is critically depending on the balance between activating and inhibitory T cell surface receptors. Such balance is lost in a number of chronic inflammatory skin conditions and is the main scope of this project. Therefore, we want to find out, if certain surface receptors of cytotoxic T cells in inflammatory skin diseases with a lot of activated and damaging cytotoxic T cells (so called interface and lichenoid dermatoses) contributing to the disease. This project consists of a multidisciplinary team of clinicians, computational scientists and molecular biologists and will combine expertise in inflammatory skin diseases, cutaneous immunology, and CD8+ T cell function to investigate the contribution of certain activation and inhibitory receptors to the dysregulation of cytotoxic T cell. We will first recruit patients with the respective skin diseases. T cells of the skin and blood are analysed based on their receptor expression using new technology that allows for a broad view on genes that are transcribed in individual cells (so called single-cell and spatial transcriptomics). We will then assess with functional readout systems the properties of candidate receptors of cytotoxic T cells and assess their relevance in various aspects. With this project, we expect reveal the role of activating and inhibitory surface receptors of T cells in cutaneous inflammation. Our patient-centered experimental approach will provide insight in the mechanisms leading to cutaneous inflammation. The combination of original models and analytical approaches developed through the project will help to find new therapeutic strategies in future.