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Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (ATAC-seq)

ABSTRACT: Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (ATAC-seq)

PROVIDER: PRJNA635691 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11869478_1.fastq.gz	Fastqsanger.gz
	SRR11869478_2.fastq.gz	Fastqsanger.gz
	SRR11869479_1.fastq.gz	Fastqsanger.gz
	SRR11869479_2.fastq.gz	Fastqsanger.gz
	SRR11869480_1.fastq.gz	Fastqsanger.gz

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Erythrophagocytosis drives anti-inflammatory programming of liver macrophages

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Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (Bulk RNA seq SPTA CD40 mac)

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Erythrophagocytosis drives anti-inflammatory programming of liver macrophages [Agilent]

Project description: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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Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (ATAC-seq)

Project description: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. Mapping transposase-accessible chromatin in single cells using sequencing (scATAC-seq) suggested NFE2L2/NRF2 as a critical driver of anti-inflammatory erythrophagocytes in the livers of hemolytic mice and heme-suppression of the inflammatory response was abolished in macrophages from Nfe2l2/Nrf2-deficient animals. 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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Erythrophagocytosis drives anti-inflammatory programming of liver macrophages

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-08-13 | GSE145244 | GEO

Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (Bulk RNA seq BMDMs)

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Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (Bulk RNA seq SPTA CD40 mac)

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