Homeostatic chemokines as putative therapeutic targets in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal chronic interstitial lung disease (ILD) that affects lung mechanical functions and gas exchange. IPF is caused by in-creased fibroblast activity and collagen deposition that compromise the alveo-lar-capillary barrier. Identifying an effective therapy for IPF remains a clinical challenge. Chemokines are key proteins in cell communication that have func-tions in immunity as well as in tissue homeostasis, damage, and repair. Chemo-kine receptor signaling induces the activation and proliferation of lung-resident cells, including alveolar macrophages (AMs) and fibroblasts. AMs are an impor-tant source of chemokines and cytokines during IPF. We highlight the complexity of this system and, based on insights from genetic and transcriptomic studies, propose a new role for homeostatic chemokine imbalance in IPF, with implica-tions for putative therapeutic targets.