Research ArticleMACROPHAGES

Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties

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Science Immunology  27 Mar 2020:
Vol. 5, Issue 45, eaax8756
DOI: 10.1126/sciimmunol.aax8756

Airway-hugging macrophages

Effective immune defense in the lungs relies on myeloid cells that phagocytose, process, and present foreign substances that enter the airways including pathogens. Ural et al. studied a subset of pulmonary interstitial macrophages expressing CD169 that are predominantly found within the bronchovascular tree. These nerve- and airway-associated macrophages (NAMs) are self-renewing, yolk sac–derived cells requiring colony-stimulating factor 1 (CSF1) for their development. NAMs serve an immunoregulatory role during responses to lung inflammation. These findings provide a deeper insight into the specialized myeloid subsets that contribute to maintaining pulmonary homeostasis.


Tissue-resident macrophages are a diverse population of cells that perform specialized functions including sustaining tissue homeostasis and tissue surveillance. Here, we report an interstitial subset of CD169+ lung-resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AMs). They are primarily localized around the airways and are found in close proximity to the sympathetic nerves in the bronchovascular bundle. These nerve- and airway-associated macrophages (NAMs) are tissue resident, yolk sac derived, self-renewing, and do not require CCR2+ monocytes for development or maintenance. Unlike AMs, the development of NAMs requires CSF1 but not GM-CSF. Bulk population and single-cell transcriptome analysis indicated that NAMs are distinct from other lung-resident macrophage subsets and highly express immunoregulatory genes under steady-state and inflammatory conditions. NAMs proliferated robustly after influenza infection and activation with the TLR3 ligand poly(I:C), and in their absence, the inflammatory response was augmented, resulting in excessive production of inflammatory cytokines and innate immune cell infiltration. Overall, our study provides insights into a distinct subset of airway-associated pulmonary macrophages that function to maintain immune and tissue homeostasis.

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