TRPM5 ION CHANNEL INFLUENCE ON T LYMPHOCYTE ACTIVATION IN A MURINE MODEL OF TYPE 1 DIABETES MELLITUS

• Grant number: 23/02889-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• Status: Discontinued
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Pietro Luigi Lebani
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM
• Associated scholarship(s): 24/21545-0 - The role of the TRPM5 channel in MAIT and T cell activation in type 1 diabetes, BE.EP.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 advancement of studies on the functions of 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 functioning as a taste receptor from the family of long transient receptors (TRPs). TRPM5 is sensitive to changes in intracellular calcium levels and modulates the entry of this ion. Calcium influx into lymphocytes determines several stimulatory signaling pathways at the intracellular level. Recently, a study demonstrated that the presence of TRPM5 in B lymphocytes is related to the activation of these cells and that the absence of this receptor inhibits responses triggered by the binding of an antigenic stimulus to the B cell receptor (BCR). It was also shown that steviol glycosides, chemical compounds obtained from the South American plant Stevia rebaudiana and marketed under the generic name of stevia in sweeteners, could activate TRPM5 in pancreatic ² cells, inducing the production of insulin and attenuating hyperglycemia in animals with type 2 diabetes mellitus (DM2). However, we still know little about the effects of these ion channels on the T lymphocyte response and how these channels are expressed and activated in these cells. The work proposed here seeks to understand the role of the TRPM5 receptor in the activation of T lymphocytes using a model that mimics an experimental autoimmune disease. For this, we will evaluate the TRPM5 receptor role in the context of the development of type 1 diabetes mellitus (DM1) induced by streptozotocin (STZ) in TRPM5 receptor knockout animals. In addition to the activation of TCD4+ and TCD8+ lymphocytes, we will evaluate the peripheral glucose tolerance in these animals, the production of serum insulin, and the morphological aspects of the pancreas of diabetic animals. We will also use a group of WT animals with induced DM1 that will receive steviol to stimulate the activity of the TRPM5 receptor. This project aims to show new strategies to combat and control inflammatory diseases through non-canonical immunological receptors, such as TRPM5.