Metabolic characterization of Foxp3+ RORgt+ T cell population in the experimental model of Colitis-associated colorectal Cancer

• Grant number: 18/24350-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2019
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Marcella Cipelli
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM
• Associated scholarship(s): 21/11012-6 - Effects of the Pseudomonas aeruginosa quorum sensing molecule 3-oxo-C12-HSL on T cell activation in lung epithelial cell 3D organoids, BE.EP.DD

Abstract

Colorectal Cancer (CRC) is responsible for 700,000 people deaths worldwide each year, being the fourth most deadly Cancer. The risk of developing this type of Cancer is closely associated with diet and lifestyle of the individual, showing a higher incidence in people who ingest red meat in excess and do not engage in any type of physical activity. In addition to these factors, chronic ulcerative colitis has also been associated with an increased risk of CRC, specifically classified as colitis-associated Colorectal Cancer (CAC). In this case, inflammatory factors are related to carcinogenesis, disease progression and even metastasis. Recently, a population of Foxp3+ RORgt+ T cells was identified in the region of the lamina propria of colon, which is dependent on the interaction with microbiota and identified as an immunosuppressive component in CAC. However, its metabolic profile as well as its participation during the progression of CAC has not yet been clarified. Thus, our hypothesis is that the inflammatory microenvironment observed in the experimental model of CAC is essential for the definition of the metabolic program of Foxp3+ RORgt+ T cells, since it is expected that genetic deletion of the HIF-1a component, regulated by mTOR pathway in Foxp3+ T cells modulates the susceptibility of animals to disease. In this study, we will characterize metabolically, emphasizing the signaling pathways currently known as determinants in the differentiation of Th17 and Foxp3+ T cell populations, and, immunologically, the role of Foxp3+ RORgt+ T cells in the experimental model of CAC. We hope to generate innovative data that can add knowledge to the current literature and can substantiate better therapies for patients with CAC. (AU)

Scientific publications

(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)

CIPELLI, MARCELLA; DA SILVA, ELOISA MARTINS; CAMARA, NIELS OLSEN SARAIVA. Gut Microbiota Resilience Mechanisms Against Pathogen Infection and its Role in Inflammatory Bowel Disease. CURRENT CLINICAL MICROBIOLOGY REPORTS, v. 10, n. 4, p. 11-pg., 2023-10-07. (20/14388-4, 17/05264-7, 18/24350-4)