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| Status |
Public on Aug 13, 2020 |
| Title |
Erythrophagocytosis drives anti-inflammatory programming of liver macrophages [Agilent] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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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 |
A two color common reference design was chosen with 3-5 independent biological replicates of each condition. Each experimental sample (Cy5 labeled) was hybridized against a non-treated reference sample (Cy3 labeled).
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| Contributor(s) |
Schaer CA, Pfefferlé M, Ingoglia G, Schaer DJ, Vallelian F |
| Citation(s) |
32663195 |
| |
| Submission date |
Mar 01, 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
|
| City |
Schlieren |
| State/province |
Schweiz |
| ZIP/Postal code |
8952 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL10333 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version) |
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| Samples (18)
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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 |
PRJNA609562 |
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