The role of the TRPM5 channel in MAIT and T cell activation in type 1 diabetes

• Grant number: 24/21545-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: May 01, 2025
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Pietro Luigi Lebani
• Supervisor: Agnes Lehuen
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Institut Cochin, France
• Associated to the scholarship: 23/02889-7 - TRPM5 ION CHANNEL INFLUENCE ON T LYMPHOCYTE ACTIVATION IN A MURINE MODEL OF TYPE 1 DIABETES MELLITUS, BP.IC

Abstract

Initially described for their role in taste and their abundant presence in oral cavity cells, taste receptors are chemoreceptors activated by environmental molecules that generate a response in the form of an electrical impulse, which is processed by the nervous system and creates the perception of taste. With the advance of studies on taste receptors, their presence in ectopic regions was demonstrated, suggesting more diverse roles than initially believed. We know that taste receptors are present in several organs and perform essential functions, such as controlling the secretion of hormones by the pancreas. TRPM5 (long transient receptor potential channel 5) is a channel/receptor from the family of long transient receptors (TRPs). As a taste receptor, it is sensitive to changes in intracellular calcium levels and negatively modulates the entry of this ion. Considering this function for immune cells, especially for lymphocytes, the calcium influx determines several stimulatory signaling pathways at the intracellular level. Recently, a study demonstrated that the presence of TRPM5 in B lymphocytes regulates the activation of these cells, and the absence of this receptor enhances the response triggered by the binding of an antigenic stimulus to the B cell receptor (BCR). However, we still know little about the effects of these ion channels on other lymphocyte subpopulations. The proposed project seeks to understand the TRPM5 role in the activation and function of T lymphocytes and MAIT cells, in the context of diabetes mellitus type 1 (DM1). By using flow cytometry, we want to analyze the expression of this receptor in human blood peripheral T lymphocytes and MAIT cells, in healthy and DM1 patients. In addition, we want to evaluate the impact of the TRPM5 in the metabolism of human CD4 and CD8 T lymphocytes and MAIT cells and the peripheral cytokines production in these patients. This project aims to show new strategies to combat and control inflammatory diseases such as DM1 through non-canonical immunological receptors, such as TRPM5.