ArticleThe Journal of clinical investigation2021
The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging.
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Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 1% of its field
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Who cites it
122 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis.BMC biology · 2026Pooled it
- Monocytes in pneumonia: Functional plasticity and innate memory (Review).International journal of molecular medicine · 2026Review
- Alveolar Macrophages: Development, Respiratory Homeostasis, Signal Pathways, Diseases, and Therapeutic Opportunities.MedComm · 2026Review
- CpG content contributes to tissue-resident macrophage enhancer selection.Nucleic acids research · 2026Article
- Cellular hallmarks and aging clock of the human lung parenchyma.Nature communications · 2026Article
- Differential activation of NF-Κβ and HIF-1α between fetal liver-derived and myeloid-derived macrophages drives inflammatory differences followingInfection and immunity · 2026Article
- Ageing-associated regenerative failure in the lung: stem cell senescence and transitional cell persistence in idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- Immunosenescence in systemic and multi-organ aging: mechanisms, inter-organ crosstalk, and translational opportunities.npj aging · 2026Review
- Epigenetic de-repression of basal cell metaplasia in aging AT2 cells is a risk factor for idiopathic pulmonary fibrosis (IPF).bioRxiv : the preprint server for biology · 2026Article
- NF-κB-activated fibroblasts orchestrate inflammaging and emergence of pro-inflammatory granzyme KImmunity · 2026Article
- Myeloid-derived alveolar-like macrophages are a tractable model to understand the role of ontogeny in alveolar macrophage functionbioRxiv : the preprint server for biology · 2026Article
- Pathogen-specific host responses define distinct pneumonia endotypes in the human lung.bioRxiv : the preprint server for biology · 2026Article
- Testosterone protects from metabolic syndrome-associated lung dysfunction in a high-fat diet rabbit model.Endocrinology · 2026Article
- Telomere damage-mediated senescence in alveolar epithelial type II cells but not in macrophages aggravates inflammation in acute lung injury.Respiratory research · 2026Article
- Chronic IL-21 exposure reshapes pulmonary environment, elevating risk of respiratory diseases.Cellular and molecular life sciences : CMLS · 2026Article
- Respiratory virus immune response in the aged host.Immunity & ageing : I & A · 2026Review
- Sex-associated transcriptional changes to synovial macrophages in the aging joint.Frontiers in immunology · 2026Article
- Immunosenescence and susceptibility to respiratory viruses: a state-of-the-art review.European respiratory review : an official journal of the European Respiratory Society · 2026Review
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 3 institutions in 2 countries.
Alexandra C McQuattie-PimentelDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Ziyou RenDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Nikita JoshiDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Satoshi WatanabeDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Thomas StoegerDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.
Monica ChiDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Ziyan LuDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Lango SichizyaDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Raul Piseaux AillonDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Ching-I ChenDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Saul SoberanesDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Zhangying ChenDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Paul A ReyfmanDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
James M WalterDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Kishore R AnekallaDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Jennifer M DavisDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Kathryn A HelminDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Constance E RunyanDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Hiam Abdala-ValenciaDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Kiwon NamDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Angelo Y MelitonDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, University of Chicago Hospitals, Chicago, Illinois, USA.
Deborah R WinterDepartment of Medicine, Division of Rheumatology, Northwestern University, Chicago, Illinois, USA.
Richard I MorimotoDepartment of Biochemistry and Molecular Genetics, Northwestern University, Evanston, Illinois, USA.
Gökhan M MutluDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, University of Chicago Hospitals, Chicago, Illinois, USA.
Ankit BharatDepartment of Surgery, Division of Thoracic Surgery, Northwestern University, Chicago, Illinois, USA.
Harris PerlmanDepartment of Medicine, Division of Rheumatology, Northwestern University, Chicago, Illinois, USA.
Cara J GottardiDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Karen M RidgeDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Navdeep S ChandelDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Jacob I SznajderDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
William E BalchThe Scripps Research Institute Department of Chemical Physiology, La Jolla, California, USA.
Benjamin D SingerDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Alexander V MisharinDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
G R Scott BudingerDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
Northwestern University · USUniversity of Chicago · USScripps Research Institute · US
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MRole of LUBAC and Na K-ATPase in Acute Lung InjuryP01HL071643 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHANDEL, NAVDEEP S · 2003 to 2019
$30.8MTissue resident macrophages regulate proteostasis in the aging lungP01AG049665 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GR Scott Budinger · 2015 to 2026
$26.9MTechnology CoreU19AI135964 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ALAN R HAUSER · 2018 to 2026
$24.7MThe proteasome in aging and neurodegenerative diseaseP01AG054407 · NIA · NORTHWESTERN UNIVERSITY · PI FINKBEINER, STEVEN M · 2018 to 2022
$14.0MPilot Program CoreP30ES027792 · NIEHS · UNIVERSITY OF CHICAGO · PI Gokhan M. Mutlu, Gail S Prins · 2017 to 2026
$13.6MTraining Program In Lung SciencesT32HL076139 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KAREN M RIDGE, Jacob I Sznajder · 2004 to 2026
$9.6MRole of alveolar macrophages in particulate matter-induced cardiopulmonary diseaseR01ES015024 · NIEHS · UNIVERSITY OF CHICAGO · PI MUTLU, GOKHAN M. · 2006 to 2022
$6.1MRole of spleen educated monocytes in mediating ischemia-reperfusion injury followinglung transplant surgeryR01HL147575 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ankit Bharat, GR Scott Budinger · 2019 to 2026
$5.5MPathogenesis of lung injury mediated by lung-restricted antibodiesR01HL147290 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ankit Bharat, GR Scott Budinger · 2019 to 2026
$5.2MDonor nonclassical monocytes mediate primary graft dysfunction and remote organ injury following lung transplant surgeryR01HL145478 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ankit Bharat, GR Scott Budinger · 2019 to 2026
$4.8MMechanisms of regulatory T cell-mediated recovery from severe viral pneumoniaR01HL149883 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Benjamin David Singer · 2020 to 2026
$4.1MCSRD VA I01 CX001777NCI NIH HHS P30 CA060553NHLBI NIH HHS K08 HL128867NHLBI NIH HHS K08 HL146943NHLBI NIH HHS P01 HL071643NHLBI NIH HHS R01 HL134375NHLBI NIH HHS R01 HL134800NHLBI NIH HHS R01 HL145478NHLBI NIH HHS R01 HL147290NHLBI NIH HHS R01 HL147575NHLBI NIH HHS R01 HL149883NHLBI NIH HHS R01 HL153312NHLBI NIH HHS R01 HL154686NHLBI NIH HHS R56 HL135124NHLBI NIH HHS T32 HL076139NIAID NIH HHS U19 AI135964NIAMS NIH HHS R01 AR073270NIAMS NIH HHS R21 AR074902NIA NIH HHS K99 AG068544NIA NIH HHS P01 AG049665NIA NIH HHS P01 AG054407NIA NIH HHS R37 AG026647NIA NIH HHS RF1 AG057296NIEHS NIH HHS P30 ES027792NIEHS NIH HHS R01 ES015024NIEHS NIH HHS U01 ES026718NIH HHS S10 OD011996
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.
Indexed as
AgingAnimalsCellular MicroenvironmentHumansLungMacrophages, AlveolarMiceMice, TransgenicRNA-SeqAgingImmunologyInfluenzaInnate immunityMacrophages
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.