Despite advancement in treatments and the benefits in lung function from the modulator therapies, chronic lung inflammation has detrimental effects on lives of people with cystic fibrosis (CF). However, specific therapies to reduce the inflammatory burden are still missing.
This project aims to investigate unexplored pathways of the inflammation-based pathology, in order to provide innovative therapeutic options for CF care.
In CF, platelets (PLT) are hyperactivated and malfunctioning, contributing to lung inflammation and slowing down the beneficial mechanisms of its resolution. PLT modulate inflammation via both direct (i.e., production of inflammatory mediators) and indirect actions through the formation of PLT-CD8 T lymphocytes aggregates (PLA) that modulate leukocyte actions.
Evidence suggests that people with CF (pwCF) generate insufficient T-cell responses that contribute to support the excessive inflammation. However, how PLT affect CD8 and what is the impact of PLT-CD8 crosstalk on airway inflammation is still unexplored.
The hypothesis is that this crosstalk may contribute to sustain the vicious circle of chronic inflammation and persistent infection in CF lungs
To investigate the role and interaction of PTL/CD8 aggregates, researchers will use cells purified from blood of people with CF, the recently developed CF airway-on-chip (see project GMSG#1/2023) and in vivo mouse models. The analysis will be conducted in collaboration with FFC Ricerca CFaCore and Servizio Colture Primarie.
The results may reveal unexpected pharmacological targets to counter regulate CF inflammation and lung damage. Furthermore, this project will also generate new knowledge about the role of platelets and CD8 T lymphocytes, paving the way for new research aimed at dissecting their function in CF.