Descripción del proyecto
La interacción de las células inmunitarias con el nicho de las células madre epiteliales en el páncreas
Los linfocitos T reguladores (Treg) pueden modular las células madre epiteliales, que son fundamentales para la homeostasis y la regeneración tisular. Indicios recientes sugieren que las células linfoides innatas de tipo 2 (ILC2, por sus siglas en inglés) contribuyen a la proliferación de los Treg y, por lo tanto, podrían influir en el nicho de las células madre epiteliales. El trabajo anterior del proyecto PanILC, financiado con fondo europeos, demostró que la activación de las ILC2 en el páncreas aumenta los efectivos de Treg, lo que indica una posible interacción entre las dos poblaciones celulares. Durante PanILC, sus investigadores se centrarán en el papel y la diafonía de las ILC2 y los Treg en la pancreatitis. Dado que la pancreatitis constituye un factor de riesgo importante para el desarrollo de cáncer de páncreas, los resultados del proyecto proporcionarán conocimientos relevantes sobre el papel de estos tipos celulares en el desarrollo de tumores.
Objetivo
Regulation of the epithelial stem cell compartment is critical for tissue homeostasis and regeneration. Consequently, imbalance in this process, through acquisition of somatic mutations for instance, may give rise to tumorigenesis. Emerging reports reveal that regulatory T cells (Tregs) can modulate epithelial stem cell dynamics in the skin, while type 2 innate lymphoid cells (ILC2s) are known to influence tissue-regeneration. Recent work in our laboratory has elucidated that ILC2s crosstalk is essential for local Tregs expansion. We hypothesize that tissue-resident ILC2s influence the stem cell niche by recruiting and regulating Tregs, and that such a mechanism could be key to tissue regeneration as well as tumor development.
Preliminary data in the lab suggest that the intraperitoneal injection of the potent ILC2 inducer IL-33 in mice activates ILC2 in the pancreas, and that a concomitant increase in Treg numbers is observed in this organ. This raises the possibility of the existence of a crosstalk between ILC2s and Tregs in the pancreas upon inflammation, such as in the case of pancreatitis. Given the considerable attention brought lately on the ability of Tregs to develop tissue-promoting capacities, we postulate that regeneration of the exocrine pancreas following pancreatitis may be driven by such pancreatic Tregs upon their “priming” by ILC2.
The present project will therefore focus on understanding the role of ILC2 and Tregs and their possible crosstalk in pancreatitis development, as well as in the regeneration process that follows, i.e. the interaction of these immune cells with epithelial progenitors. As pancreatitis is a major risk factor for the development of pancreatic cancer, the resulting observations will then be extended to the analysis of the role of ILC2/Treg crosstalk in tumor development in an orthotopic mouse model of pancreatic tumours as well as in a genetic mouse model of pancreatic adenocarcinoma.
Ámbito científico
- medical and health sciencesclinical medicineoncologyprostate cancer
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineoncologypancreatic cancer
- medical and health sciencesbasic medicinephysiologyhomeostasis
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
CB2 1TN Cambridge
Reino Unido