Shaping gut microbiota and immune system by the intestinal epithelial cells: from tissue homeostasis to diseases

• Grant number: 19/14755-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: February 01, 2020
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Vinicius de Andrade Oliveira
• Grantee: Vinicius de Andrade Oliveira
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Santo André , SP, Brazil
• City of the host institution: Santo André
• Associated researchers: LETICIA ANDERSON BASSI ; Luciana Campos Paulino ; Marcela Sorelli Carneiro Ramos ; Mariane Tami Amano ; Niels Olsen Saraiva Câmara
• Associated scholarship(s): 25/00759-4 - The role of enteroendocrine cells in modulating intestinal inflammation, BP.MS; 24/09768-3 - Impact of the interaction between macrophages and intestinal epithelial cells on the development of intestinal inflammation, BP.DR; 25/06209-6 - Standardization of genotyping of different transgenic animals for crossbreeding in the cre-lox system, BP.TT; + associated scholarships 22/08362-8 - Biology of enteroendocrine cells in homeostasis and during intestinal inflammation, BP.DD; 21/03913-3 - Influence of obesity on the mechanisms of peripheral tolerance and on the modulation of immune response in the small intestine of mice., BP.DR; 21/10908-6 - Enteroendocrine hormones and cells of the immune system: impact on the metabolism, differentiation, and function, BP.MS - associated scholarships

Abstract

Intestinal homeostasis is a product of a complex and regulated network among diet, microbiota, gut epithelial cells and the immune system. The great challenge for the gastrointestinal tract is to respond to pathogens and to food antigen while it needs to keep its function, such as nutrient absorption, and to tolerate foreign antigens. Any disturb between these interactions unleashes an inflammatory process that has been associated with a plethora of diseases. Large efforts focusing the role of the interface between gut microbiota and immune system allowed us to understand to impact of gut microbiota in the developing of immune cells and how this contribute for the onset of several diseases, ranging from local inflammatory bowel disease to distant and systemic diseases such as cardiovascular, type 2 diabetes and metabolic syndrome. Despite that, less attention was given to the cross-talk among enteroendocrine cells (EECs), immune system and gut microbiota. EECs are cells scattered throughout the intestinal epithelium and can secrete more than twenty hormones, among them GIP and GLP, once they sense nutrients and microbiota metabolites. Thus, EECs may have a paracrine effect on surrounding immune cells within the gut, but also and endocrine effect. But how EECs interact with immune cells and gut microbiota and what are their impacts on intestinal and non-intestinal diseases are still unknown. Here, we hypothesized that EECs play an essential role in gut homeostasis, either by modulating immune cells and/or gut microbiota composition. To address this question, we will take an advantage to use sophisticated genetic mouse model to isolate an/or eliminating EECs by using cre-lox system or tamoxifen-inducible manner the context of inflammatory bowel diseases (colitis), during gut pathogen infection model and to tolerate antigen and generating regulatory T cells. We will further in vitro explore how the absence of these cells impacts the structure and function of the other cells, such as Goblet and Paneth cells. Finally, we will generate organoids in the absence of EECs cells to evaluate their impact in organoid formation structure and functioning regarding the secretion of mucus, antimicrobial peptide and what is the contribution of their secreted hormones in organoid generation. We believe that this project will expand the knowledge about the intricate interaction among all these components in the gastrointestinal tract, which in the future will contribute for new target for therapeutic purposes. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, ELOISA MARTINS; YARIWAKE, VICTOR YUJI; ALVES, RENAN WILLIAN; DE ARAUJO, DANIELE RIBEIRO; ANDRADE-OLIVEIRA, VINICIUS. Crosstalk between incretin hormones, Th17 and Treg cells in inflammatory diseases. Peptides, v. 155, p. 13-pg., 2022-07-04. (19/14755-0, 20/14388-4)

NETO, JOSE ARIMATEA DE OLIVEIRA NERY; YARIWAKE, VICTOR YUJI; CAMARA, NIELS OLSEN SARAIVA; ANDRADE-OLIVEIRA, VINICIUS. Enteroendocrine cells and gut hormones as potential targets in the crossroad of the gut-kidney axis communication. FRONTIERS IN PHARMACOLOGY, v. 14, p. 20-pg., 2023-10-19. (21/03913-3, 19/14755-0, 17/05264-7, 22/08362-8)

BERTRAM, JOHN F.; CULLEN-MCEWEN, LUISE A.; ANDRADE-OLIVEIRA, VINICIUS; CAMARA, NIELS OLSEN SARAIVA. The intelligent podocyte: sensing and responding to a complex microenvironment. NATURE REVIEWS NEPHROLOGY, v. 21, n. 7, p. 14-pg., 2025-05-08. (19/14755-0, 23/07482-2)

BASSO, PAULO JOSE; ANDRADE-OLIVEIRA, VINICIUS; CAMARA, NIELS OLSEN SARAIVA. Targeting immune cell metabolism in kidney diseases. NATURE REVIEWS NEPHROLOGY, v. 17, n. 7, APR 2021. (15/26682-6, 19/14755-0)

QUADROS-PEREIRA, LAURA; NERY-NETO, JOSE ARIMATEA DE OLIVEIRA; DA SILVA, ELOISA MARTINS; DORETTO-SILVA, LORENA; YARIWAKE, VICTOR YUJI; CAMARA, NIELS OLSEN; ANDRADE-OLIVEIRA, VINICIUS. Treatment with sitagliptin exacerbates the M2 phenotype in macrophages in vitro. International Immunopharmacology, v. 145, p. 13-pg., 2024-12-10. (17/05264-7, 21/03913-3, 19/14755-0, 20/14388-4, 22/08362-8, 21/10908-6)

DE OLIVEIRA NERY NETO, JOSE ARIMATEA; YARIWAKE, VICTOR YUJI; DA SILVA, ELOISA MARTINS; VIEIRA, RAQUEL; SOUZA, CLAUDIA SILVA; YAMADA, SUEMY MELIM; HONORIO DA SILVA, JOAO VINICIUS; CIPELLI, MARCELLA; OLIVEIRA, SAMUEL DOS SANTOS; QUADROS-PEREIRA, LAURA; et al. Chronic intestinal inflammation predisposes to the development of acute kidney injury. European Journal of Immunology, v. 54, p. 1-pg., 2024-09-01. (22/08362-8, 19/14755-0)

ANDRADE-OLIVEIRA, VINICIUS; FORESTO-NETO, ORESTES; CAMARA, NIELS OLSEN SARAIVA. Editorial: Global excellence in renal pharmacology 2022: Central and South America. FRONTIERS IN PHARMACOLOGY, v. 14, p. 3-pg., 2024-01-09. (19/02893-9, 22/01226-1, 19/14755-0, 17/05264-7)