IL-25/IL-33/TSLP contributes to idiopathic pulmonary fibrosis: Do alveolar epithelial cells and (myo)fibroblasts matter?

We suggest a novel modality in terms of IL-25/IL-33/TSLP's pro-fibrotic role in IPF. First, IL-25/IL-33/TSLP fully activates (myo)fibroblasts in fibroblastic foci (FF) in a paracrine-dependent manner. (IL-25/IL-33/TSLP)+alveolar epithelial cells-(IL-25R/IL-33R/TSLPR)+ (myo)fibroblasts axis may contribute greatly to the abnormal epithelial-mesenchymal crosstalk and lung fibrosis. Second, IL-25/IL-33/TSLP causes significant injury and phenotypic changes of alveolar epithelial cells in an autocrine-dependent manner. By acting directly on the two most important cells in the fibrotic process, i.e. alveolar epithelial cells and (myo)fibroblasts, we support the notion that biological therapies targeting IL-25/IL-33/TSLP will shed new light on the cure of IPF patients.