The role of ionotropic glutamate receptor NMDAR on CD4+ and CD8+ alpha-beta T cells and gamma-delta T cells from mouse intestinal mucosa

• Grant number: 21/06508-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 04, 2021
• End date: October 29, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jean Pierre Schatzmann Peron
• Grantee: Marília Garcia de Oliveira
• 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: 18/10242-5 - The role of ionotropic glutamate receptor NMDA in innate and adaptive immune cells from intestinal mucosa in murine experimental model, BP.DR

Abstract

The intestinal mucosa is responsible for harboring a large part of lymphocytes found in all body and together with other cells of the immune system present mainly in the region of the lamina propria play important roles in local tolerance to microorganisms of the microbiota and food antigens. In addition to the mucosa, the small and large intestines also present the submucosal layer, the muscular layer, and the serous membrane. There are present in the submucosal and muscle layers ganglionic enteric plexuses formed by networks of interconnection between neurons of the enteric nervous system. These neurons secrete various inhibitory and excitatory neurotransmitters, including glutamate, and their innervations reach the lamina propria. Recently, it has been discovered that innate and adaptive immune cells express receptors for neurotransmitters, including the glutamate ionotropic receptor NMDAR, expressed on T cells. In this context little is known about the role of NMDAR in alpha-beta T cells from intestinal mucosa. Thus, this project aims to contribute to the Ph.D. main project (#2018/10242-5) in which the main goal is to investigate whether the deficiency of NMDAR specifically on alpha-beta T cells promotes changes in the distribution and in functional profile of both innate and adaptive immune cells within intestinal intraepithelial and lamina propria compartments, as well as changes in the intestinal microbiota composition. Our preliminary data thus far showed a decrease in the frequency of CD4+ T cells and an increase in the frequency of CD8+ T cells in the intestinal draining mesenteric lymph nodes as well as a decrease in the frequency of CD8+ T cells in the intraepithelial compartment of the small intestine of CD4crexGrin1flox compared to their littermate controls, evidencing the relevance of the studies to be conducted in the research fellowship abroad. (AU)