GM-CSF effects on efferocytosis and macrophage metabolism

• Grant number: 19/24771-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2020
• Effective date (End): February 28, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Pedro Manoel Mendes de Moraes Vieira
• Grantee: João Victor Virgilio da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases, AP.JP

Abstract

The study of immune cell metabolism has resulted in a major advance in understanding the immune system regulation under both physiological and pathological conditions. There is a constant metabolic adaptation so leukocytes can survive, proliferate and perform their functions. Depending on the energy and biosynthetic needs, different leukocytes and their subtypes acquire different metabolic profiles. Mitochondria play a central role in this immunometabolic regulation of leukocytes. In addition to regulating macrophage activation, mitochondrial dynamics and mitochondrial membrane potential are essential in modulating macrophage effector functions, such as in the production of reactive oxygen species and cytokines. Among the different effector functions of macrophages in the maintenance of tissue homeostasis, one of the main ones is the removal of apoptotic cells, in a process known as efferocytosis. The speed and efficiency of this process are important to prevent pro-inflammatory signals release, autoantigens recognition, and autoimmune disease development. GM-CSF treatment on bone marrow-derived macrophages increases their efferocytosis capacity, increasing the number of apoptotic cells that can be phagocyted. GM-CSF is a molecule with a largely recognized by different types of cells, acting mainly through STAT5 phosphorylation and there is limited knowledge about the metabolic response to GM-CSF. We aim to determine the GM-CSF/STAT5-mediated immunometabolic changes required for macrophage efferocytosis modulation. (AU)