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Cited by 48Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisTransplantation: Methods and OutcomesOccupational and environmental lung diseases

Dynamic atlas of immune cells reveals multiple functional features of macrophages associated with progression of pulmonary fibrosis

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Lv, Jiaoyan, Gao, Haoxiang, Ma, Jie, Liu, Jiachen, Tian, Yujie, Yang, Chunyuan, Li, Mansheng, Zhao, Yue +5 more·2023·Frontiers in Immunology
DOI 10.3389/fimmu.2023.1230266PMC PMC10525351
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Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high mortality rate and unclarified aetiology. Immune response is elaborately regulated during the progression of IPF, but immune cells subsets are complicated which has not been detailed described during IPF progression. Therefore, in the current study, we sought to investigate the role of immune regulation by elaborately characterize the heterogeneous of immune cells during the progression of IPF. To this end, we performed single-cell profiling of lung immune cells isolated from four stages of bleomycin-induced pulmonary fibrosis—a classical mouse model that mimics human IPF. The results revealed distinct components of immune cells in different phases of pulmonary fibrosis and close communication between macrophages and other immune cells along with pulmonary fibrosis progression. Enriched signals of SPP1, CCL5 and CXCL2 were found between macrophages and other immune cells. The more detailed definition of the subpopulations of macrophages defined alveolar macrophages (AMs) and monocyte-derived macrophages (mo-Macs)—the two major types of primary lung macrophages—exhibited the highest heterogeneity and dynamic changes in expression of profibrotic genes during disease progression. Our analysis suggested that Gpnmb and Trem2 were both upregulated in macrophages and may play important roles in pulmonary fibrosis progression. Additionally, the metabolic status of AMs and mo-Macs varied with disease progression. In line with the published data on human IPF, macrophages in the mouse model shared some features regarding gene expression and metabolic status with that of macrophages in IPF patients. Our study provides new insights into the pathological features of profibrotic macrophages in the lung that will facilitate the identification of new targets for disease intervention and treatment of IPF.

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Authors
Lv, J., Gao, H., Ma, J., Liu, J., Tian, Y., Yang, C., Li, M., Zhao, Y., Li, Z., Zhang, X., Zhu, Y., Zhang, J., & Wu, L.
Affiliations
  • Center for Life Sciences (CN)
  • Beijing National Research Center for Information Science and Technology (CN)
  • Beijing Proteome Research Center (CN)
  • Annoroad Gene Technology (China) (CN)
Corresponding author
  • Zhang, Xuegong
  • Zhu, Yunping
  • Zhang, Jianhong
  • Wu, Li
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2023-09-13
Volume
14
Pages
1230266-1230266
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2023.1230266
PMC
PMC10525351
OpenAlex
W4386709908
Cited by
48
References
61
Citations by year
2026: 17 · 2025: 18 · 2024: 13
FWCI
8.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (31991174, 61721003, 62250005)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
Keywords
idiopathic pulmonary fibrosis, macrophages, alveolar macrophages, monocyte-derived macrophages, immune cell heterogeneity, bleomycin-induced lung fibrosis, disease progression, GPNMB, TREM2, osteopontin, RANTES, CXCL2, single-cell profiling, lung immune cells
MeSH terms
Animals, Humans, Lung, Macrophages, Membrane Glycoproteins, Receptors, Immunologic, Macrophages, Alveolar, Disease Progression, Mice, Idiopathic Pulmonary Fibrosis

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