Th17 Cell Role in Intestinal Permeability and Adipose Tissue Inflammation in Obesity and Metabolic Syndrome in experimental model

• Grant number: 24/09974-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Daniela Carlos Sartori
• Grantee: Sara Cândida Barbosa
• Supervisor: Ari Waisman
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Johannes Gutenberg University Mainz (JGU), Germany
• Associated to the scholarship: 21/13597-1 - Evaluation of the therapeutic potential of Lactococcus lactis expressing IL-17 in Obesity-induced type 2 Diabetes, BP.DR

Abstract

Obesity, a chronic condition with multiple causes, predisposes individuals to metabolic syndrome (MetS) and type 2 diabetes (T2D) by disrupting energy balance through lipid accumulation and the infiltration of inflammatory cells into adipose tissue (AT) named meta-inflammation. A high-fat diet (HFD) is linked to decreased levels of intestinal Th17 cells and segmented filamentous bacteria (SFB) that promote Th17 responses. In line with these findings, our initial results indicate that reduced gene and protein IL-17 expression in diet-induced obese mice (DIO) correlates with increased intestinal permeability. We propose that Th17 cell adoptive transfer could restore the intestinal balance, reduce permeability, and thereby alleviate metabolic consequences and inflammation in visceral adipose tissue (VAT). Our goal is to investigate how Th17 cells and IL-17 impacts in intestinal permeability and inflammation in VAT using an experimental model of obesity and MetS. First, we intend to analyze the profile cellular and molecular in the ileum and VAT of the absence of IL-17A/F in knockout (KO) mice at different life stages like young or old mice (6 and 18 weeks of age). Th17 cells isolated from Foxp3GFPRorcRFP reporter mice also will be transferred to mice induced with HFD-induced obesity and MetS. Following cell transfer, we will evaluate clinical and metabolic parameters, inflammatory, intestinal permeability, and the expression of tight junction proteins. Flow cytometry will analyze profile of pro- and anti-inflammatory (M1 and M2) macrophages and neutrophils in VAT, as well as Th17 lymphocyte and neutrophil populations in the lamina propria. Finally, we will measure gene and protein IL-17 and IL-22 expression in the ileum via RT-PCR and ELISA after Th17 cell adoptive transfer. Understanding the implication of the absence of IL-17A/F and this intervention may offer valuable insights for managing obesity and MetS under HFD conditions.