Clinical and experimental studies of tolerance mechanisms in the thymus aiming at therapeutic targeting of the thymus in the treatment of autoimmune diseases

Immune dysregulation is a key feature of many diseases, e.g. autoimmunity and cancer, and even though the thymus is of vital importance for immune regulation, therapeutic tools to target thymic function are lacking.

The overall objective of the project is to to study mechanisms of central tolerance induction in the thymus with the aim to develop novel therapeutic methods that target the thymus to antigen specific central tolerance in the treatment of autoimmune diseases.

A broad translational approach is applied with four sub-projects in which clinical and experimental, in vitro and in vivo, studies are combined.Specific aims:To clinically and experimentally characterize primary thymic disorders; autoimmune polyendocrine syndrome type 1, Down syndrome, 22q11 deletion syndrome and neonatal thymectomy.To explore sex differences in thymic central tolerance induction and their relevance for the development of autoimmune diseaseTo perform transcriptional and functional characterization of thymic B cells, with focus on their role in central tolerance induction.To test the hypothesis that thymic exosomes can be used therapeutically to target the thymus and induce antigen specific central tolerance in the treatment of autoimmune diseases.

In the projects, we are utilizing a combination of a unique access to human thymus, experimental front-line methodology, clinical studies, animal models and a well-defined patient material to address a central scientific and clinical problem.