Epi_UNCOV

Acrónimo: Epi_UNCOV

Objetivo temático: By modulating RA signals, we will determine its impact inTCRαβDN T cell generation.

By tackling the molecular link between micronutrients and unconventional TCRαβDN T cells we are deepening our understanding in transcriptional, gut homing and specific function programs that govern this still elusive cell type.

We also believe that our work will provide insights into intestinal mucosa homeostasis and tumour immune microenvironment, as colorectal cancer. This will pave the way for new prognostic biomarkers and potential targets for innovative treatments such as immunotherapy, which is still emerging for colorectal cancer. The cutting edge of the questions addressed and solid preliminary data in this proposal make us anticipate that our results will be published in high-ranking journals.

Área Científica: Medical and Health Sciences; Clinical Medicine, Immunology and Infection

Síntese do Projeto: Colorectal cancer is the third most common cancer in both sexes worldwide and ranks second in terms of mortality. Besides an ageing population and unfavorable risk factors, as such chronic inflammation and dietary factors (low consumption of fruits, vegetables, and fibre and high consumption of processed meat) increase the risk of colorectal cancer.

Intestine provides absorption of nutrients and water, but is exposed to massive challenges. Intraepithelial lymphocyte (IEL) subsets living amid epithelium affords the gut with protection against pathogens and immunoregulatory mechanisms, granting mucosal homeostasis. Recently, IELs were implicated in systemic metabolism. Amongst the major subsets of IELs are the unconventional CD4-CD8β- (DN) αβ T cell subset (hereafter called TCRαβDN), which can express the homotypic CD8αα molecule. TCRαβDN T cells are a subset of immune cells that are at the crossroad between innate and adaptive immunity. These cells display na “active but resting” phenotype at the intestinal epithelium and present an immune-regulatory facet under pathological conditions Thus, suggesting putative tumour immunosuppression function. Unconventional TCRαβDN IELs derive from thymic IEL precursors (IELp) being pre-programmed with an innate-like effector program and pre-imprinted with gut tropism at the thymus. While other unconventional T cells (iNKT and MAIT cells) have been largely characterized, fundamental biological features of the TCRαβDN T cells remain currently elusive. In fact, despite advances in recent years, critical aspects of TCRαβDN T cell biology are still largely unknown: i) the transcriptional program that govern TCRαβDN T cells; ii) the factors regulating thymic gut tropism iii) environmental factors regulating these cells; iv) their specific function; and v) as well as relevant pathways operating in newly identified human equivalent TCRαβDN T cells.

Investigador Responsável na UC: Manuela Cristina Fernandes Ferreira

Unidade Orgânica UC: Reitoria - CNC

Instituições participantes no projeto: Universidade de Coimbra

Instituição Financiadora/Gestora: FCT

Programa de Financiamento: FCT - PTDC/IC&DT 2022

Período de execução: De 01/03/2023 a 28/02/2026 (36 meses)

Custo total elegível (EUR): 243 537,04 €

Apoio financeiro público nacional: 243 537,04 €

Técnico do Projeto: Kayleigh Mikaela Oliveira Rodrigues

Contacto: 239247021 (Ext 210021)