Influence of obesity on the mechanisms of peripheral tolerance and on the modulation of immune response in the small intestine of mice.

• Grant number: 21/03913-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2022
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vinicius de Andrade Oliveira
• Grantee: Victor Yuji Yariwake
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/14755-0 - Shaping gut microbiota and immune system by the intestinal epithelial cells: from tissue homeostasis to diseases, AP.JP

Abstract

Epidemiological studies have shown an association between obesity and autoimmune diseases. However, the immunologic mechanisms that explain this association have not been elucidated. The small intestine is one of the most important organs for the induction of peripheral tolerance; the intestinal immune system maintains the function of the organ while it responds to antigens from diet, pathogens and microbiota. Thus, our hypothesis is that obesity impacts the intestinal homeostasis and lead to the loss of peripheral tolerance that can be associated with the triggering of autoimmune diseases. To investigate this hypothesis, the aim of the project is to evaluate whether obesity exerts influence on the mechanisms of peripheral tolerance in a murine model of oral tolerance. OT-II mice will be fed with high-fat diet and submitted to a protocol of oral tolerance to ovalbumin (OVA). They will be challenged with OVA-expressing bacteria to evaluate whether peripheral tolerance is altered. Quantification and characterization of the main cells involved in oral tolerance (dendritic cells and regulatory T cells) will be performed and we will study the specific effects of regulatory FOXP3+ T cells and microbiota in this context of loss of peripheral tolerance. To further investigate the mechanisms involved in the crosstalk among diet, microbiota, epithelium and intestinal immune system we will focus on the incretin GLP-1 as a possible modulator of immune activity in the small intestine. We hope that the results will contribute to a better understanding of the complex interactions in intestinal mucosa that can be involved with autoimmune diseases.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NETO, JOSE ARIMATEA DE OLIVEIRA NERY; YARIWAKE, VICTOR YUJI; CAMARA, NIELS OLSEN SARAIVA; ANDRADE-OLIVEIRA, VINICIUS. Enteroendocrine cells and gut hormones as potential targets in the crossroad of the gut-kidney axis communication. FRONTIERS IN PHARMACOLOGY, v. 14, p. 20-pg., 2023-10-19. (21/03913-3, 19/14755-0, 17/05264-7, 22/08362-8)

QUADROS-PEREIRA, LAURA; NERY-NETO, JOSE ARIMATEA DE OLIVEIRA; DA SILVA, ELOISA MARTINS; DORETTO-SILVA, LORENA; YARIWAKE, VICTOR YUJI; CAMARA, NIELS OLSEN; ANDRADE-OLIVEIRA, VINICIUS. Treatment with sitagliptin exacerbates the M2 phenotype in macrophages in vitro. International Immunopharmacology, v. 145, p. 13-pg., 2024-12-10. (17/05264-7, 21/03913-3, 19/14755-0, 20/14388-4, 22/08362-8, 21/10908-6)