Effect of inulin diet on migration and function of intestinal gamma-delta T cells

• Grant number: 23/02507-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: September 01, 2023
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Helder Carvalho de Assis
• Supervisor: Daniel de Sousa Mucida
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Rockefeller University, United States
• Associated to the scholarship: 20/00311-0 - Role of ³´ T cells in adaptations of intestinal epithelium induced by inulin diet, BP.DD

Abstract

Fermentation of inulin fiber is known to induce IL-22 production, enhancing barrier function and epithelial regeneration. Gamma-delta T cells in the gut produce IL-22 and interact directly with IECs through the Myd88 axis. Furthermore, gamma-delta cells can sense nutrients from the diet, reprogramming their activity depending on the diet composition. Although the inulin diet has shown effects on immunity and the gut, few studies showed how gamma-delta cells respond to inulin and inulin-enriched microbiota. Our previous data have shown that inulin-fed mice have genes differentially expressed in gamma-delta T cells of the small intestine, presenting a downregulation of inflammatory genes and upregulation of pathways associated with metabolism and HIF-1. Furthermore, inulin-fed mice presented a proliferative effect of intestinal stem cells (ISCs) of the caecum and colon. These effects are lost in IL-22-/- and TCR´-/- but not in Ahr”Ror³T mice suggesting that the phenotype is mediated by gamma-delta cells and IL-22 signaling. Although we observed a correlation between gamma-delta cells, IL-22, and the proliferative phenotype of ISCs, more investigation is needed to describe the immunological circuit involved. Therefore, in this project, we intend to clarify how gamma-delta T cells respond to the inulin-induced microenvironment and its role in proliferative phenotype by ISCs. Data generated in this project will allow us to understand the impact of inulin on gut immunity and how it changes the profile of ISCs. Finally, the findings may provide new insights into therapeutic utilizations for inulin in the maintenance of gut homeostasis. (AU)