Myeloid-mesenchymal crosstalk drives ARG1-dependent profibrotic metabolism via ornithine in lung fibrosis.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung remodeling and collagen deposition that leads to respiratory failure. Myeloid cells are abundant in IPF lung and in murine lung fibrosis, but their functional effects are incompletely understood. Using mouse and human lung models, we show that ornithine produced by myeloid cells expressing arginase 1 (ARG1) serves as a substrate for proline and collagen synthesis by lung fibroblasts. The predominant ARG1-expressing myeloid cells in mouse lung were macrophages, but in IPF lung, high-dimensional imaging revealed ARG1 was expressed mainly in neutrophils. Small-molecule ARG1 inhibition suppressed both ornithine levels and collagen expression in cultured, precision-cut IPF lung slices and in murine lung fibrosis. These results

SUBMITTER: Yadav P 

PROVIDER: S-EPMC12578403 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature