Effects of Aryl Hydrocarbon Receptor (AHR) modulation on the activation and metabolism of macrophages in lean and obese mice

• Grant number: 20/02573-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2021
• End date: January 04, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Pedro Manoel Mendes de Moraes Vieira
• Grantee: Bianca Gazieri Castelucci
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 20/16030-0 - Immunometabolic adaptation of tissue resident macrophages in health and disease, AP.TEM
• Associated scholarship(s): 22/16000-9 - Search for a new therapeutic target for modulating macrophage activation during obesity: the role of Ahr signaling, BE.EP.PD

Abstract

Macrophages are present in most tissues of vertebrates and play a key role in both host defense and control of tissue homeostasis. These phagocytes can sense tissue microenvironment and detect foreign microorganisms by either the interaction with Pathogen-Associated Molecular Patterns (PAMPs) or tissue injury by its interaction with Damage-Associated Molecular Patterns (DAMPs). Recently, Aryl Hydrocarbon Receptor (AHR) was pointed as one of the main regulators in immune cells development and function, having a direct impact on effective macrophage polarization to both pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Beyond AHR function as an environment sensor, that receptor can interact with signaling from the Toll-Like Receptors (TLRs) and adjust macrophage activity in response to specific DAMPs and PAMPs. Recent studies with AHR-null mice showed that AHR deficiency protects mice against diet-induced Obesity. These findings suggest that AHR signaling may be a key factor in Obesity development, a disorder strongly related to changes in adipose tissue environment that promote an increment in both M1 population and activation. Despite AHR activity as an environmental sensor and its ability to control macrophages polarization, to date, it is unknown how the modulation of AHR affects the activation and metabolism of homeostatic or obese Adipose Tissue Macrophages (ATM). Nowadays, Obesity affects over 650 million adult people worldwide, which demands the understanding of the key mechanisms responsible for Obesity progression to discover new therapies against the disease. Therefore, this study aims to elucidate AHR function in the activation and the metabolism determination of macrophages exposed to different Obesity related PAMPs and the AHR role in homeostatic and obese ATM activation and metabolic profile determination. (AU)