ABSTRACT
Pulmonary fibrosis is an interstitial lung disease caused by various factors such as exposure to workplace environmental contaminants, drugs, or X-rays. Epithelial cells are among the driving factors of pulmonary fibrosis. Immunoglobulin A (IgA), traditionally thought to be secreted by B cells, is an important immune factor involved in COVID-19 infection and vaccination. In current study, we found lung epithelial cells were involved in IgA secretion which, in turn, promoted pulmonary fibrosis. The spatial transcriptomics and single-cell sequencing suggests that Igha transcripts were highly expressed in the fibrotic lesion areas of lungs from silica-treated mice. Reconstruction of B-cell receptor (BCR) sequences revealed a new cluster of AT2-like epithelial cells with a shared BCR and high expression of genes related to IgA production. Furthermore, the secretion of IgA by AT2-like cells were trapped by extracellular matrix and aggravated pulmonary fibrosis by activating fibroblasts. Targeted blockade of IgA secretion by pulmonary epithelial cells may be a potential strategy for treating pulmonary fibrosis.