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The role of ionotropic glutamate receptor NMDA in innate and adaptive immune cells from intestinal mucosa in murine experimental model

Grant number: 18/10242-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2019
Effective date (End): June 30, 2022
Field of knowledge:Biological Sciences - Immunology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Jean Pierre Schatzmann Peron
Grantee:Marília Garcia de Oliveira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

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 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 was discovered that several cells of the immune system including innate and adaptive cells have receptors for neurotransmitters, even the ionotropic glutamate receptor NMDAR. It is known that glutamate performs its functions through the binding to their receptors which are expressed by several cells within different organs, not only the neurons in the central nervous system. Thus, the present study intends to evaluate whether the deficiency of NMDAR specifically in ±²T cells is able to promote changes in the intestinal mucosal barrier, as well as alter not only the activation profile of these cells but also of all other cellular populations present on lamina propria given their interrelationships. This could imply an imbalance of local tolerance to the microbiota and a greater susceptibility to intestinal inflammatory diseases such as Colitis, be these autoimmune or infectious. Our preliminary results already show a change in the frequency of CD8+T cells and macrophages in the mesenteric lymph nodes of CD4crexGrin1flox mice evidencing the relevance of the studies to be conducted. (AU)