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Nat Immunol. 2020 Feb;21(2):221-231. doi: 10.1038/s41590-019-0582-z. Epub 2020 Jan 20.

Transcriptomic and epigenetic mechanisms underlying myeloid diversity in the lung.

Author information

1
Department of Pediatrics, University of California San Diego, Rady Children's Hospital, La Jolla, CA, USA. esajti@health.ucsd.edu.
2
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
3
Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
4
Department of Cellular & Molecular Medicine, Bioscience Research Laboratories, University of Arizona, College of Medicine, Tucson, AZ, USA.
5
Department of Medicine, Division of Quantitative Life Sciences, Meakins-Christie Laboratories, McGill University Health Centre, Montreal, Quebec, Canada.
6
Department of Pediatrics, University of California San Diego, Rady Children's Hospital, La Jolla, CA, USA.
7
Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Abstract

The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly understood. In the present study, systematic evaluation of transcriptomes and open chromatin of alveolar macrophages (AMs), interstitial macrophages (IMs) and lung monocytes from two mouse strains enabled inference of common and cell-specific transcriptional regulators. We provide evidence that these factors drive selection of regulatory landscapes that specify distinct phenotypes of AMs and IMs and entrain qualitatively different responses to toll-like receptor 4 signaling in vivo. These studies reveal a striking divergence in a fundamental innate immune response pathway in AMs and establish a framework for further understanding macrophage diversity in the lung.

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PMID:
31959980
DOI:
10.1038/s41590-019-0582-z

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