How do T cells survive at the site of inflammation?- Metabolic mapping of tissue-resident memory T cells in rheumatic diseases

Chronic autoimmune diseases such as rheumatoid arthritis (RA) and myositis represent a clinical challenge due to inadequate treatment response and the recurrence of symptoms.

During the last decade, new immunosuppressive drugs have been introduced, considerably improving the management of rheumatic diseases but prolonged drug-free remission is rarely achieved.

We and other groups have shown that tissue-resident memory (TRM) T cells reside in inflammatory tissues and persist even despite immunosuppressive treatment.

Although they are suspected to participate in relapses and disease chronicity, it is unclear how they survive in the inflammatory milieu and which molecular pathways they use to resist immunosuppressive drugs. Moreover, there is currently no drug specifically targeting TRM T cells.

My hypothesis is that TRM T cells rely on specific metabolic pathways which favor their persistence in inflammatory tissues.

In this project, we will single cell map TRM T cell metabolism using an ongoing single T-cell analysis platform on biopsies from the synovial joint (RA) and the muscle tissues (myositis) combined with new metabolomics tools. We will also investigate if endurance exercise and therapeutic interventions modify TRM T cell metabolism.

Our goal is to generate knowledge on the mechanisms involved in tissue residency which would create the basis for a new generation of targeted therapies