Characterize the susceptibility of T lymphocytes for ferroptosis in obesity.

• Grant number: 23/08241-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Ana Paula Campanelli
• Grantee: Luiza Maria Fernandes
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Experimental and clinical evidence points to a correlation between chronic inflammation and the development of obesity and/or complications arising from this condition. One of the factors that can lead to the development of disorders and diseases is inflammation; when inflammation and obesity occur simultaneously, we observe more significant changes in the immune system. CD4+ T cells participate in the crosstalk between the immune system and adipose tissue, regulating inflammation and metabolism in obesity. Increased cholesterol induces functional exhaustion of cytotoxic CD8+ T cells (CTLs). It is known that exhausted CD8+ T cells promote lipid peroxidation of tumor and infected cells and sensitize these cells to ferroptosis via IFN³. Recently, the expression of CD36, a molecule related to fatty acid transport, increases the susceptibility of CD8+ T cells to ferroptosis, impairing cytokine production and cytotoxic activity of these cells. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, has been implicated in a broad set of biological contexts, from development to aging, immunity, and cancer. Considering that inflammation associated with obesity can be detrimental to the development of an efficient immune response, the present project aims to investigate the susceptibility of T lymphocytes for ferroptosis in obesity.