Dissecting the role of TRPM5 in ¿¿T (gamma-delta) cell function at the gut-brain axis interface

• Grant number: 25/11561-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 20, 2025
• End date: September 19, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: João Vinícius Honório da Silva
• Supervisor: Rafael Machado Rezende
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Brigham and Women's Hospital (BWH), United States
• Associated to the scholarship: 22/14364-3 - The role of the TRPM5 receptor in the activation and differentiation of CD4+ T cells and its relevance in an experimental model of intestinal inflammation, BP.DR

Abstract

Transient receptor potential melastatin 5 channel (TRPM5) is a polymodal ion channel expressed in different cells of the body, including chemosensory and immune cells. It is an ion channel impermeable to calcium (Ca2+) but is activated by increased intracellular Ca2+. Ca2+ is an important intracellular second messenger for several cellular functions, especially in immune cells. Preliminary data suggest that TRPM5 deficiency alters ¿¿T cell frequency in the intestinal epithelium and mesenteric lymph nodes, potentially impacting mucosal immunity, microbiota sensing, and systemic behavior. ¿¿T cells are a subset of unconventional T cells that play an important role in innate and adaptive immunity, and are critical in barrier immunity and have emerging roles in neuroimmune modulation. Therefore, this project aims to uncover how TRPM5 influences ¿¿T cell development and function and how this shapes gut-brain communication and behavior. For this, in vivo experiments will be performed with male C57BL/6 Wild-type and TRPM5 knockout mice. We will develop techniques to investigate the phenotypic and developmental impact of TRPM5 absence in ¿¿T cells. In addition, we will assess the functional role of ¿¿T cells and TRPM5 in gut immunity and behavioral responses, and further identify transcriptional signatures of ¿¿T cells modulated by TRPM5 in the context of the gut-brain axis. The results obtained in this project will contribute to the understanding of the biology of ¿¿T cells and the mechanism of action of TRPM5 in ¿¿T lymphocytes and in the pathogenesis of IBD, in addition to opening perspectives for future therapeutic interventions. (AU)