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Immunity. 2017 Nov 21;47(5):913-927.e6. doi: 10.1016/j.immuni.2017.10.006. Epub 2017 Nov 14.

Tissue-Resident Macrophages Are Locally Programmed for Silent Clearance of Apoptotic Cells.

Author information

1
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
2
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
3
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
4
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Electronic address: barton@berkeley.edu.

Abstract

Although apoptotic cells (ACs) contain nucleic acids that can be recognized by Toll-like receptors (TLRs), engulfment of ACs does not initiate inflammation in healthy organisms. Here we identified macrophage populations that continually engulf ACs in distinct tissues and found that these macrophages share characteristics compatible with immunologically silent clearance of ACs; such characteristics include high expression of AC recognition receptors, low expression of TLR9, and reduced TLR responsiveness to nucleic acids. Removal of the macrophages from tissues resulted in loss of many of these characteristics and the ability to generate inflammatory responses to AC-derived nucleic acids, suggesting that cues from the tissue microenvironment program macrophages for silent AC clearance. The transcription factors KLF2 and KLF4 control the expression of many genes within this AC clearance program. The coordinated expression of AC receptors with genes that limit responses to nucleic acids might ensure maintenance of homeostasis and thus represent a central feature of tissue macrophages.

KEYWORDS:

KLF2; KLF4; Toll-like receptors; apoptotic cell clearance; autoinflammation; macrophage

PMID:
29150239
PMCID:
PMC5728676
DOI:
10.1016/j.immuni.2017.10.006
[Indexed for MEDLINE]
Free PMC Article

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