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| Status |
Public on Nov 15, 2017 |
| Title |
Resident Macrophages are Locally Programmed for Silent Clearance of Apoptotic Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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. To better understand this phenomenon, we identified and characterized macrophage populations that continually engulf ACs in several distinct tissues. These macrophages share characteristics compatible with immunologically silent clearance of ACs, including high expression of AC recognition receptors, low expression of TLR9, and reduced TLR responsiveness to nucleic acids. When removed from tissues, these macrophages lose many of these characteristics and generate inflammatory responses to AC-derived nucleic acids, suggesting that cues from the tissue microenvironment are required to program macrophages for silent AC clearance. We show that KLF2 and KLF4 control expression of many genes within this AC clearance program. Coordinated expression of AC receptors with genes that limit responses to nucleic acids may represent a central feature of tissue macrophages that ensures maintenance of homeostasis.
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| Overall design |
RNA sequencing on purified Tim-4+ peritoneal macrophages was performed on RNA isolated from macrophages immediately ex vivo (n=1) or after tissue culture for 60 hours (n=2) in two independent experiments. Tim-4+ peritoneal macrophages were stimulated + apoptotic cells (ACs) after tissue culture for 2 or 60 hours n=2 per experimental condition.
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| Contributor(s) |
Roberts AW, Lee BL, Deguine J, John S, Shlomchik MJ, Barton GM |
| Citation(s) |
29150239 |
| Submission date |
Jan 18, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Gregory M Barton |
| E-mail(s) |
barton@berkeley.edu
|
| Organization name |
University of California, Berkeley
|
| Street address |
University of California, Berkeley Dept. of Molecular and Cell Biology 142 LSA #3200
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| City |
Berkeley |
| State/province |
CA |
| ZIP/Postal code |
94720 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA362496 |
| SRA |
SRP097011 |
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