Characterization of Intestinal and Circulating Regulatory T Cell Subpopulations During Crohn's Disease and Experimental Model of Intestinal Inflammation

• Grant number: 25/13704-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2025
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Raphael Sanches Peres
• Grantee: Sofia Lírio Santos Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/17817-1 - Identification of cell interactions that affect regulatory T cells function in inflammatory bowel diseases, AP.JP

Abstract

Foxp3+ regulatory T cells (Tregs) play a crucial role in maintaining immune homeostasis. Disruption of this homeostasis can result in inflammatory bowel disease (IBD), a condition characterized by chronic inflammation of the gastrointestinal tract. Changes in the composition and function of Treg subsets may underlie IBD in certain patients. However, the heterogeneity of Tregs and their interactions with other intestinal cells in IBD remain poorly understood. Different Treg subpopulations exist in the intestine, each with distinct characteristics and suppressive functions. Tregs act in concert with a diverse network of cells, and these interactions are essential for tissue adaptation and acquisition of their suppressive functions.The relevance of Treg subsets during intestinal inflammation, disease remission, and therapeutic response is not yet fully characterized. Previous data obtained during the principal investigator's postdoctoral research provide evidence that intestinal Tregs increase the protein expression of KLRB1 (CD161) following anti-TNF treatment in IBD patients who respond to this therapy, which is the first-line biological treatment used for IBD. The Treg population expressing CD161 is associated with tissue repair, but the molecular mechanisms governing this subpopulation and the acquisition of this phenotype are still poorly understood.Other data have also identified a Treg subpopulation with high gene expression of the FCRL3 receptor in the circulation of IBD patients. Tregs expressing FCRL3 have been described as defective in modulating inflammatory processes in tissues and are associated with disease activity in patients with rheumatoid arthritis.In this context, the present project aims to characterize human and murine Treg cell subsets during intestinal inflammation. Human Treg subpopulations will be characterized, focusing on CD161 and FCRL3 expression, using peripheral blood and surgical resection samples from patients with Crohn's disease (CD) and healthy controls, through spectral flow cytometry. Additionally, intestinal and splenic Treg subpopulations will be characterized in animals subjected to a colitis model induced by Helicobacter hepaticus infection combined with IL-10 signaling blockade.Thus, this project will provide relevant information on the different Treg subpopulations found in the intestine and circulation during intestinal inflammation and homeostasis in humans and mice, generating new perspectives for the development of therapeutic strategies targeting Tregs in Crohn's disease. (AU)