The role of enteroendocrine cells in modulating intestinal inflammation

• Grant number: 25/00759-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Vinicius de Andrade Oliveira
• Grantee: Milena Santos Alves da Silva
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , 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

Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic disorders characterized by inflammation of the gastrointestinal tract, resulting in debilitating symptoms such as diarrhea, abdominal pain, and weight loss, significantly impacting patients' quality of life. The intestine plays a crucial role in both digestion and immune response, acting as a complex interface between the body and the external environment. Its structure is compartmentalized and multifaceted, encompassing elements such as the microbiota, intestinal epithelial cells (IECs), mucus, and the mucosal immune system, with the harmony of these components being essential for intestinal homeostasis. IECs, originating from intestinal crypts, are specialized for various functions, including nutrient absorption, mucus secretion, and defense against microorganisms. A subpopulation of IECs consists of enteroendocrine cells (EECs), which play a central role by secreting hormones and peptides that influence not only intestinal homeostasis but also communication between the gut and the immune system. Interestingly, EEC dysfunction appears to be associated with the exacerbation of these conditions, leading to abnormal immune responses and imbalances in hormone secretion. However, the mechanisms underlying this exacerbation have not yet been thoroughly investigated. Thus, the aim of this study is to explore how EEC dysfunction contributes to the pathogenesis of ulcerative colitis and investigate the effects of increasing the number of these cells on disease prognosis. In this context, understanding the role of EECs in UC is fundamental for developing new therapeutic approaches aimed at restoring intestinal homeostasis. To achieve this, we will culture colonic intestinal organoids derived from stem cells, which will be induced to differentiate into EECs using a cocktail of specific inhibitors. The use of intestinal organoids to induce EECs represents an innovative strategy, allowing for detailed investigation of cellular interactions in an environment that mimics the physiological conditions of the intestine. This project could unveil the molecular mechanisms regulating the inflammatory response through IECs, offering new possibilities for more effective and personalized treatments for IBDs. (AU)