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Biology of enteroendocrine cells in homeostasis and during intestinal inflammation

Grant number: 22/08362-8
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): August 01, 2022
Effective date (End): January 31, 2025
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Vinicius de Andrade Oliveira
Grantee:José Arimatéa Oliveira Nery Neto
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


Inflammatory bowel diseases have an increased incidence worldwide. They can occur due to several factors, from genetic to after infections by pathogenic microorganisms. Furthermore, intestinal inflammation may be associated with the development of colorectal cancer. Thus, it becomes important to understand the processes and components related to intestinal homeostasis as well as those related to the modulation of inflammatory processes in the intestine. The intestine is composed of a complex interconnected network of immune and non-immune cells, intestinal microbiota and intestinal epithelial cells, all interacting harmoniously to maintain intestinal homeostasis. Disturbances in this communication have been associated with the development and/or severity of inflammatory bowel diseases. Despite the great advance in knowledge about the interaction between intestinal immune cells and the intestinal microbiota in different types of diseases, little attention has been paid to intestinal epithelial cells. Enteroendocrine Cells (EECs) are a subtype of cells residing in the epithelial layer of the gastrointestinal tract. EECs are located along the intestinal epithelium and although they comprise 1% of all epithelial cells, they are considered an important endocrine system of the host. EECs play a major role in the release of hormones from the perception of nutrients in the intestinal lumen, such as carbohydrates, amino acids and lipids and from microbiota and/or their products. EECs differ from a common intestinal precursor and, throughout their differentiation process, are distinguished from other secretory cells such as Paneth and Goblet cells by the expression of a set of specific transcription factors such as Neurogenin-3, Neuro D1 and later Pax4 and Pax6. The first two are crucial in the process of differentiating EECs while the last two are responsible for the production of hormones. Recently, it was observed that the absence of EECs leads to an impairment in the absorption of lipids, which suggests that EECs participate directly in the host's metabolism, and that their absence impairs the absorption of nutrients. But the role of EECs in intestinal homeostasis as well as during inflammatory processes has not yet been investigated. Thus, the hypothesis of our work is that the absence of EECs must impair intestinal homeostasis, therefore, exacerbate the inflammatory process. (AU)

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