Cited by 177Genetics, Aging, and Longevity in Model OrganismsImmune responses and vaccinationsImmune cells in cancer

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging

Open access
McQuattie-Pimentel, Alexandra C., Ren, Ziyou, Joshi, Nikita, Watanabe, Satoshi, Stoeger, Thomas, Chi, Monica, Lu, Ziyan, Sichizya, Lango +26 more·2021·Journal of Clinical Investigation

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.

Integrity signals

Registry

Crossref · 10.1172/jci140299

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The pathogenic role of Mo-AMs in lung fibrosis is largely attributed to their production of pro-fibrotic mediators such as TGF-β, PDGF-α, osteopontin, and MMPs.

    “The pathogenic role of Mo-AMs in lung fibrosis has been largely attributed to their activity in producing a number of pro-fibrotic mediators, such as TGF-β, PDGF-α, osteopontin (OPN), and MMPs1,3,11,13,15,18,28.”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
McQuattie-Pimentel, A. C., Ren, Z., Joshi, N., Watanabe, S., Stoeger, T., Chi, M., Lu, Z., Sichizya, L., Aillon, R. P., Chen, C.-I., Soberanes, S., Chen, Z., Reyfman, P. A., Walter, J. M., Anekalla, K. R., Davis, J. M., Helmin, K. A., Runyan, C. E., Abdala-Valencia, H., Nam, K., Meliton, A. Y., Winter, D. R., Morimoto, R. I., Mutlu, G. M., Bharat, A., Perlman, H., Gottardi, C. J., Ridge, K. M., Chandel, N. S., Sznajder, J. I., Balch, W. E., Singer, B. D., Misharin, A. V., & Budinger, G. R. S.
Affiliations
  • Northwestern University (US)
  • University of Chicago Medical Center (US)
  • Scripps Research Institute (US)
Venue
Journal of Clinical Investigation
Published
2021-02-15
Volume
131
Issue
4
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
OpenAlex
W3133294399
Cited by
177
References
56
Citations by year
2026: 30 · 2025: 35 · 2024: 31 · 2023: 30 · 2022: 34 · 2021: 17
FWCI
10.01
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • NIH (AG490665, HL135124,AG049665,AI135964, HL071643,HL14575)
  • Veterans Administration (CX01777)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
alveolar macrophages, lung aging, lung microenvironment, extracellular matrix, hyaluronic acid, macrophage proliferation, influenza A virus infection, GM-CSF signaling, bone marrow-derived macrophages, lineage tracing, parabiosis, single-cell transcriptomics
MeSH terms
RNA-Seq, Aging, Animals, Humans, Lung, Mice, Transgenic, Macrophages, Alveolar, Mice, Cellular Microenvironment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review