Resident B cell function in Brown Adipose Tissue

• Grant number: 24/21630-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Licio Augusto Velloso
• Grantee: Ana Luísa Gallo Ferraz
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

The brown adipose tissue (BAT) has an important role in the thermoregulation of homeotherms. In response to cold, brown adipocytes promote uncoupled mitochondrial respiration, which results in heat production. In the last decade, studies have demonstrated that, in addition to its thermogenic activity, the BAT participates in the endogenous regulation of lipid and glucose levels, and that there is a clinical relation between the presence of active BAT and protection against diabetes and cardiovascular diseases. Sympathetic signals play a central role in the functional regulation of BAT; however, resident and recruited immune cells also participate in this regulation. Most of the studies that evaluated the participation of immune cells in the regulation of BAT focused on monocytes and macrophages. However, according to recent studies in which single-cell RNA-seq methods were used, it was demonstrated that B lymphocytes constitute the main subpopulation of immune cells in BAT. Few studies have evaluated the function of B lymphocytes in BAT; apparently, the presence or absence of these cells does not interfere with the thermogenic capacity of the tissue; nevertheless, the early surgical removal of BAT in rodents results in an unstable immune response to certain pathogenic agents in addition to manifestations of hypersensitivity. Therefore, in this project, we aim to evaluate the function of resident B lymphocytes in BAT. Initially, we will use public databases to define the subtypes of B lymphocytes that reside in BAT. Next, in cell cultures, we will evaluate whether the activation of brown adipocytes with a sympathetic agonist can result in the production of substances that modulate B lymphocytes; or even, if there is a direct (cell-to-cell) effect of brown adipocytes on B lymphocytes. In animal models, we will evaluate the impact of surgical removal of BAT on the activity of systemic B lymphocytes. We hope that this study will contribute to advances in understanding the relationship between BAT and the immune system.