TIROTAPS - Transient Receptor Potential Melastatin-like 7 (TRPM7) in Regualation of T cell subsets and Purinering Signaling

T lymphocytes control the immune response toward pathogens or self tissues by promoting or inhibiting inflammatory destruction, respectively. A defective control of immune response to self tissues results in autoimmune diseases. Adenosine triphosphate (ATP) constitutes the source of chemical energy for the majority of cellular functions. However, ATP is also released in the extracellular space as a soluble signaling molecule, which activates purinergic receptors and stimulates the pro-inflammatory function of T lymphocytes.

Upon de novo synthesis ATP binds magnesium ions thus reducing intracellular magnesium content. The reduction in free magnesium results in opening of a channel for magnesium influx called TRPM7, which further promotes lymphocytes activation. This project is aimed at studying the so far unexplored relationship between ATP synthesis, magnesium, purinergic signaling and TRPM7 activity in shaping T cell function.

Understanding the molecular mechanisms that govern T cell responsiveness will improve our knowledge of the pathogenesis of autoimmune diseases.

This study will be performed in collaboration with Susanna Zierler from the Ludwig-Maximilians-University, Walther-Straub-Institute for Pharmacology und Toxicology, Munich, Germany and with Yuri Negulyaev from the Russian Academy of Science Institute of Cytology, St. Petersburg, Russia.