Ass. MD TP10: Immunometabolic activities of drugs used in pemphigoid diseases

While the treatment of autoimmune diseases (such as, but not limited to, pemphigoid diseases) predominantly relies on the use of corticosteroids, immunosuppressive drugs and biologics, a variety of advances have been made in the past decades. Novel therapy strategies are being developed through the emerging field of immunometabolism, which aims to exploit the immune cell metabolism to modulate inflammatory responses. The high energy demand of immune cells makes their metabolism central in all inflammatory processes. Nonetheless, the complex regulation and dependencies of immune cell activation and metabolic control require further investigation to effectively exploit key pathways for therapeutic treatments.

While the use of immunometabolic modulators has achieved promising results in animal models of autoimmune and auto-inflammatory disease (e.g. psoriasis, multiple sclerosis [EAE]), little is known in the field of autoimmune skin blistering diseases.

This project is extending previous work on the impact of metabolic modulators on inflammatory processes. The gained mechanistic insights into key pathways affected by generalized metabolic modulators like Metformin and 2-Deoxy-D-Glucose are used to evaluate more specific inhibitors and to increase the efficacy of the drug treatment as well as reduce potential off target effects in the animal model. The project aims to assess metabolic phenotypes (i.e. glycolytic activity, respiration, redox potential) and immunological phenotypes (cell differentiation, cytokine production) murine neutrophil granulocytes under various stimulations in vitro. Additionally, the use of specific metabolic inhibitors will be validated in vivo, using the autoantibody-transfer induced EBA mouse model.