Usage Information
Citation Information: J Clin Invest. 2021;131(4):e140299. https://doi.org/10.1172/JCI140299.
Abstract
Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow–derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.
Authors
Alexandra C. McQuattie-Pimentel, Ziyou Ren, Nikita Joshi, Satoshi Watanabe, Thomas Stoeger, Monica Chi, Ziyan Lu, Lango Sichizya, Raul Piseaux Aillon, Ching-I Chen, Saul Soberanes, Zhangying Chen, Paul A. Reyfman, James M. Walter, Kishore R. Anekalla, Jennifer M. Davis, Kathryn A. Helmin, Constance E. Runyan, Hiam Abdala-Valencia, Kiwon Nam, Angelo Y. Meliton, Deborah R. Winter, Richard I. Morimoto, Gökhan M. Mutlu, Ankit Bharat, Harris Perlman, Cara J. Gottardi, Karen M. Ridge, Navdeep S. Chandel, Jacob I. Sznajder, William E. Balch, Benjamin D. Singer, Alexander V. Misharin, G.R. Scott Budinger
Usage data is cumulative from May 2024 through May 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 3,072 | 943 |
| 313 | 268 | |
| Figure | 1,024 | 12 |
| Supplemental data | 202 | 28 |
| Citation downloads | 121 | 0 |
| Totals | 4,732 | 1,251 |
| Total Views | 5,983 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)