The study investigates the role of *Placenta-expressed transcript 1* (Plet1) in lung epithelial repair following influenza A virus (IAV) infection. Using high-dimensional single-cell transcriptomics, lung organoid modeling, and adoptive cell transfer experiments, the researchers found that transitioning bone marrow-derived macrophages (BMDM) and tissue-resident alveolar macrophages (TR-AM) highly express Plet1. Plet1 is released from alveolar macrophages and acts as a mediator of macrophage-epithelial cross-talk, promoting alveolar epithelial cell proliferation and resealing of the epithelial barrier. Intratracheal administration of recombinant Plet1 early in the disease course reduced viral lung injury and saved mice from fatal IAV infection, highlighting its therapeutic potential. The study reveals a novel mechanism where Plet1-expressing macrophages drive lung epithelial repair, providing a potential therapeutic target for severe viral pneumonia.The study investigates the role of *Placenta-expressed transcript 1* (Plet1) in lung epithelial repair following influenza A virus (IAV) infection. Using high-dimensional single-cell transcriptomics, lung organoid modeling, and adoptive cell transfer experiments, the researchers found that transitioning bone marrow-derived macrophages (BMDM) and tissue-resident alveolar macrophages (TR-AM) highly express Plet1. Plet1 is released from alveolar macrophages and acts as a mediator of macrophage-epithelial cross-talk, promoting alveolar epithelial cell proliferation and resealing of the epithelial barrier. Intratracheal administration of recombinant Plet1 early in the disease course reduced viral lung injury and saved mice from fatal IAV infection, highlighting its therapeutic potential. The study reveals a novel mechanism where Plet1-expressing macrophages drive lung epithelial repair, providing a potential therapeutic target for severe viral pneumonia.