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| Status |
Public on Aug 13, 2020 |
| Title |
Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (Single-cell RNA-seq SPTA mac) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Under conditions of erythrolytic stress, which accompanies many disease states, macrophages play key roles in phagocytosing damaged RBCs and preventing the toxic effects of cell-free hemoglobin and heme to maintain homeostasis. Using a genetic mouse model of spherocytosis and single-cell RNA sequencing, we show that erythrolytic stress promotes expansion of a specific macrophage population in the liver (which we named “erythrophagocytes”) expressing high levels of Marco and Hmox1 and low levels of MHC class II related genes with an anti-inflammatory gene expression signature. We confirmed the strong anti-inflammatory function of erythrophagocytes in two models of sterile inflammatory liver disease: anti-CD40 antibody-induced systemic inflammation syndrome with necrotizing hepatitis and diet-induced nonalcoholic fatty liver disease (NAFLD). The unique anti-inflammatory phenotype and function of erythrophagocytes was reproduced in vitro by heme-exposure of mouse macrophages, yielding a transcriptional profile that segregated heme-polarized from classical M1- and M2-polarized cells. The phenotype of anti-inflammatory erythrophagocytes coincided with NFE2L2/NRF2 driven gene expression and was abolished in Nfe2l2/Nrf2-deficient macrophages. Our findings point to a novel pathway that regulates macrophage functions to link RBC homeostasis and heme metabolism with innate immunity.
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| Overall design |
Liver macrophages from a sph/sph mouse and its littermate wild-type control were isolated using anti-F4/80 antibody coated dynabeads and subjected to droplet-based single-RNA sequencing (10x genomics).
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| Contributor(s) |
Pfefferlé M, Ingoglia G, Vallelian F, Schaer D |
| Citation(s) |
32663195 |
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| Submission date |
Feb 13, 2020 |
| Last update date |
Nov 27, 2020 |
| Contact name |
Marc Pfefferle |
| E-mail(s) |
marc.pfefferle@uzh.ch
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| Organization name |
University hospital Zürich (USZ)
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| Street address |
Wagistrasse 12
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| City |
Schlieren |
| State/province |
Schweiz |
| ZIP/Postal code |
8952 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE145244 |
Erythrophagocytosis drives anti-inflammatory programming of liver macrophages |
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| Relations |
| BioProject |
PRJNA606505 |
| SRA |
SRP249274 |
