期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：4
DOI：10.1073/pnas.2119759119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Submucosal glands secrete antimicrobial proteins and mucus into the airway lumen to protect the lung by killing inhaled and aspirated pathogens and clearing them from the lung. They can also contribute to several lung diseases, including the genetic disease cystic fibrosis. To better understand their structure and function, we isolated and studied submucosal glands from newborn pigs. Normal and cystic fibrosis submucosal glands were similar, suggesting that disease is due to loss of anion secretion rather than an intrinsic cell defect. By identifying submucosal gland cell types and the messenger RNA they express, the data aid understanding of submucosal gland function and provide a baseline for learning how environmental and genetic challenges contribute to lung disease.
Submucosal glands (SMGs) protect lungs but can also contribute to disease. For example, in cystic fibrosis (CF), SMGs produce abnormal mucus that disrupts mucociliary transport. CF is an ion transport disease, yet knowledge of the ion transporters expressed by SMG acini, which produce mucus, and SMG ducts that carry it to the airway lumen is limited. Therefore, we isolated SMGs from newborn pigs and used single-cell messenger RNA sequencing, immunohistochemistry, and in situ hybridization to identify cell types, gene expression, and spatial distribution. Cell types and transcript levels were the same in non-CF and CF SMGs, suggesting that loss of epithelial anion secretion rather than an intrinsic cell defect causes CF mucus abnormalities. Gene signatures of acinar mucous and acinar serous cells revealed specialized functions in producing mucins and antimicrobials, respectively. However, surprisingly, these two cell types expressed the same ion transporters and neurohumoral receptors, suggesting the importance of balancing mucin and liquid secretion to produce optimal mucus properties. SMG duct cell transcripts suggest that they secrete HCO
3
− and Cl
−, and thus have some similarity to pancreatic ducts that are also defective in CF. These and additional findings suggest the functions of the SMG acinus and duct and provide a baseline for understanding how environmental and genetic challenges impact their contribution to lung disease.
