Fig. 2

Cellular and molecular mechanisms of PD-1/PD-L1 involvement in the pathogenesis of IPF. A PD-1 mediates the up-regulation of IL-17 and TGF-β production by PD-1⁺Th17 cells through STAT3, which promotes lung fibrosis, and PD-1 inhibits the differentiation of CD4⁺T cells to Treg cells, which promotes the production of type I collagen and inhibits myofibroblast proliferation; B PD-L1 on lung fibroblasts inhibits myofibroblast proliferation by inhibiting the p53 pathway and activating the FAK pathway, causing myofibroblasts to evade phagocytosis, leading to excessive proliferation of myofibroblasts, resulting in lung fibrosis. In addition, PD-L1 mediates lung fibroblast-to-myofibroblast transformation (FMT) through Smad3 and β-catenin signaling pathways, thus promoting lung fibrosis; C PD-L1 upregulation on lung fibroblasts promotes fibrosis by inhibiting autophagy leading to myofibroblast proliferation and ECM deposition