Role of the acetate-FFAR2 axis on granulopoiesis and IL-22 production by intestinal neutrophils

• Grant number: 23/00393-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): July 03, 2023
• Effective date (End): July 02, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Sarah de Oliveira
• Supervisor: Marco Collona
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: University of Washington, United States
• Associated to the scholarship: 21/09155-3 - Analysis of the role of the FFAR2 receptor in neutrophil functionality and myelopoiesis, BP.DR

Abstract

The intestinal microbiota plays a key role in promoting hematopoiesis and generating immune cells. This modulation occurs directly by host-commensal species interaction or indirectly though metabolites derived from the microbial metabolism. Short-chain fatty acids (SCFAs) are some of these molecules that are produced from dietary fibers by gut bacteria. They mainly activate protein-coupled receptors G, such as FFAR2, that are highly expressed in hematopoietic progenitors and neutrophils. Studies using SCFAs treatment in models of intestinal inflammation indicated that acetate-FFAR2 signaling in neutrophils is crucial for mucosal immunity. However, the role of this axis on the production, maturation and function of neutrophils is still unclear. Neutrophils were recently described as also capable of producing IL-22 and regulate tissue repair; however, the relevance of IL-22-producingneutrophils is unclear, and whether SCFAs and FFAR2 can modulate it is still unknow. In this context, the aim of this project is to analyze the role of the acetate-FFAR2 axis on neutrophils granulopoiesis and their production ofIL-22 during intestinal inflammation. In particular, we will assess how microbiota-derived acetate, through its receptor FFAR2, impacts neutrophil development and how directly or indirectly modulates the epithelial cells and tissue repair through IL-22 signaling. Altogether, these data will support the hypothesis about the connection between microbiota, SCFAs and neutrophils, especially on the role of the FFAR2 receptor, and how this interaction might modify the host inflammatory response. (AU)