Study of stromal-leukocyte interactions for acetylcholine effects on immunological homeostasis in the mesentery

• Grant number: 20/11408-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2020
• End date: April 30, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Gabriela Melo da Costa Furlan
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/25364-0 - Impact of infection-induced immunological scarring on the long-term host metabolic homeostasis, AP.JP

Abstract

This fellowship is being requested for a scientific initiation student to collaborate directly for the conclusion of a subproject linked to JP assistance. The main goal of this project is to evaluate the contribution of the anti-inflammatory cholinergic pathway in the inflammation of adipose tissue and the development of diet-induced metabolic syndrome. Our previous date points out for the role of acetylcholine in the mesentery immune homeostasis. We used 3 different models do study the role of acetylcholine signaling in the mesentery immune homeostasis: 1) VACHT (vesicular transporter deficiency for acetylcholine, 2) KD (knock down) animals; 2) Pharmacological treatment with a non-selective antagonist for nicotinic acetylcholine receptors (mecamylamine), and 3) surgical ablation on the vagus nerve (cervical vagotomy). In the 3 models, there was a significant reduction in the number of leukocytes in the mesentery, particularly in naïve and non-activated cells, associated with an increase in the presence of all types of effector cells, but more significantly for cells type 2 immune cells, such as eosinophils, ILC2 and Th2. Thus, the present project has the general objective of understanding the effect of acetylcholine on the stroma of the mesentery and, consequently, on the immunological homeostasis of leukocytes in the mesentery. As specific objectives we intend to: 1) characterize the fraction of stromal cells (CD45negatives) of VACHT mice, vagotomized or treated with mecamylamine; 2) to analyze the effect of stromal cells isolated from the mesentery of VACHT mice, vagotomized or treated with mecamylamine on the activation of lymphocytes and isolated ILCs from the mesentery; 3) evaluate the effect of blockage of nicotinic receptors on stromal cell and innate and adaptive lymphocyte co-cultures.