The role of SARMI in CD4 T cell activation and differentiation

• Grant number: 22/16176-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Samuel dos Santos Oliveira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM

Abstract

Activated T cells undergo drastic cellular and metabolic reprogramming.Cells with inflammatory profiles have glycolysis as the main source of ATP production,while regulatory T cells mainly use oxidative phosphorylation to meet their energydemands. The anabolic metabolism of lymphocytes is closely related to their activation,as well as sustains their differentiation. NAD+ is extremely important in this process,since it acts as an enzymatic cofactor during glycolysis, a phenomenon that promotesincreased ATP generation and generation of biochemical intermediates important forcell growth and subsequent expansion. SARM1 may be important for the metabolictransition suffered by activated T cells, since this component, when activated, promotesNAD+depletion. Bearing in mind the importance of glycolysis for the supply of energydemands and in the availability of important macromolecules for the proliferativeactivity of activated T cells, we hypothesized that SARM1 is a key regulator of thisprocess, due to its ability to restrict the availability of NAD+to the glycolytic pathwayin activated T cells. For this, we will work with a classic model of cell differentiationand activation, measures of gene and protein expression and respirometry to answer thehypothesis. Later, we will evaluate the physiological relevance in an in vivo model ofcolitis. We hope to demonstrate that SARM1 is decisive in the fate of the T cell after itsexit from the quiescent state.