Role of enzyme-coupled TRP channels in immune cell function (RETIF)
- Sprecher: Professor Dr. Thomas Gudermann
- Einrichtung: Walther-Straub-Institut für für Pharmakologie und Toxikologie
- Förderung: seit 2012 bis 2016
"Low systemic magnesium (Mg2+) levels exacerbate pro-inflammatory diseases, suggesting a putative role of Mg2+ transport in immune system homeostasis. The Mg2+ and calcium (Ca2+) conducting transient receptor potential ion channel, TRPM7 has an indispensable, vital role in cellular physiology. TRPM7 regulates cellular and systemic Mg2+ homeostasis and is essential for immune cell differentiation, proliferation and survival. However, little is known about underlying mechanisms or the physiologic regulation of the protein’s channel or enzymatic domain. Autoimmune diseases are often accompanied by low systemic Mg2+ concentrations, which might be associated with altered TRPM7 function. Thus, it is important to identify whether TRPM7 represents a valuable new target for immune therapy. Antigen-presenting cells (APC) and T cells are pivotal regulators of immune system homeostasis. The intrinsic risk of potentially harmful autoreactive T cells is controlled centrally during selection in the thymus. Peripheral mechanisms to limit autoimmunity include immunosuppression through regulatory T cells (Tregs). In the last years Tregs received enormous attention as their deficiency provokes severe autoimmune disorders. The regulation of tissue homeostasis by APC is equally important to avoid unbalanced pro-reactive immune system responses. APC maintain tissue homeostasis via phagocytosis of invading pathogens and secretion of pro- and anti-inflammatory mediators. In this project we are planning an interdisciplinary approach combining biophysics with basic immunology to study the role of TRPM7 in APC and T cell function and in immune system homeostasis. We are going to use novel innovative tools to identify the physiologic role of the channel versus the kinase activity. This is particularly important, as the numbers of chronic inflammatory and autoimmune diseases resultant from unbalanced immune responses, such as multiple sclerosis or colitis, are continuously increasing."