IL-8 Concurrently Promotes IPF MPC Senescence and PD-L1 Expression Enabling Escape from Immune Cell Surveillance

Idiopathic pulmonary fibrosis (IPF) is a lung disease characterized by fibrosis. The study found fibrogenic mesenchymal progenitor cells (MPCs) in the lungs of IPF patients that drive fibrotic progression. The study demonstrates that DNA damage is one of the most altered functions in IPF MPCs. It was hypothesized that IL-8 promotes DNA damage-mediated senescence in IPF MPCs and found that IL-8 induces DNA damage and promotes IPF MPC senescence. The study also discovered that IL-8 promotes the upregulation of programmed death ligand 1 (PD-L1), which helps IPF MPCs elude immune cell targeted removal. Disruption of the PD-1/PD-L1 interaction limits IPF MPC-mediated fibrotic progression.