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 Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): July 01, 2019
• Effective date (End): June 30, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Jean Pierre Schatzmann Peron
• Grantee: Marília Garcia de Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 21/06508-2 - The role of ionotropic glutamate receptor NMDAR on CD4+ and CD8+ alpha-beta T cells and gamma-delta T cells from mouse intestinal mucosa, BE.EP.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 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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

POLONIO, CAROLINA MANGANELI; DE FREITAS, CARLA LONGO; DE OLIVEIRA, MARILIA GARCIA; ROSSATO, CRISTIANO; BRANDAO, WESLEY NOGUEIRA; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; NISHIYAMA MIMURA, LUIZA AYUMI; BARROS SILVA, MAYSA BRAGA; GARCIA CALICH, VERA LUCIA; et al. Murine endometrial-derived mesenchymal stem cells suppress experimental autoimmune encephalomyelitis depending on indoleamine-2,3-dioxygenase expression. Clinical Science, v. 135, n. 9, p. 1065-1082, MAY 2021. (18/10242-5, 17/22504-1, 17/11828-0, 16/07371-2, 17/26170-0)

DE FREITAS, CARLA LONGO; POLONIO, CAROLINA MANGANELI; BRANDAO, WESLEY NOGUEIRA; ROSSATO, CRISTIANO; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; DE OLIVEIRA, MARILIA GARCIA; EVANGELISTA, LUCILA PIRES; HALPERN, SILVIO; MALUF, MARIANGELA; et al. Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System. STEM CELL REVIEWS AND REPORTS, AUG 2021. (20/06145-4, 16/07371-2, 18/10242-5, 17/11828-0, 17/22504-1, 17/26170-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

OLIVEIRA, Marília Garcia de. The role of the ionotropic glutamate receptor NMDAR on α ß T cells of the intestinal mucosa in an experimental murine model. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.