The therapeutic potential of targeting immune checkpoints in IPF

Abstract

Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease with a high mortality rate. The mechanisms behind the pathophysiology of IPF development remain poorly understood. However, recent developments in fundamental and translational studies demonstrate that immune cells play a significant regulatory role in IPF. Immune players generate multiple growth factors and mediators that greatly affect the initiation and progression of IPF. Immune checkpoints are known for their capacity to regulate the intensity of immune responses. Our project aims to study the implications of these receptors in IPF. Based on a transcriptomic approach, we did identify the most relevant receptors in lung immune cells from IPF patients. Flow cytometry analyses are used to compare the expression of the identified receptors between IPF patients and healthy donors in a stratification approach. Ex-vivo experiments are also implemented to understand how the inhibition or overexpression of these receptors can impact the profibrotic activity of immune cells. In parallel, several models of transgenic mice are currently generated to investigate the implication of the identified receptors in the development of pulmonary fibrosis. Overall, this project might have the potential to uncover novel immune mechanisms leading to new diagnostic and therapeutic tools against a fatal disease.