Genomic analysis of LPS-stimulated myeloid cells identifies a common pro-inflammatory response but divergent IL-10 anti-inflammatory responses

Scientific Reports
Andrew Paul HutchinsDiego Miranda-Saavedra

Abstract

Inflammation is an essential physiological response to infection and injury that must be kept within strict bounds. The IL-10/STAT3 anti-inflammatory response (AIR) is indispensable for controlling the extent of inflammation, although the complete mechanisms downstream of STAT3 have not yet been elucidated. The AIR is widely known to extend to other myeloid cells, but it has best been characterized in macrophages. Here we set out to characterize the LPS-mediated pro-inflammatory response and the AIR across a range of myeloid cells. We found that whereas the LPS-induced pro-inflammatory response is broadly similar among macrophages, dendritic cells, neutrophils, mast cells and eosinophils, the AIR is drastically different across all myeloid cell types that respond to IL-10 (all bar eosinophils). We propose a model whereby the IL-10/STAT3 AIR works by selectively inhibiting specific pathways in distinct cell types: in macrophages the AIR most likely works through the inhibition of NF-κB target genes; in DCs and mast cells through indirect IRF disruption; and in neutrophils through IRF disruption and possibly also indirect NF-κB inhibition. In summary, no conserved IL-10/STAT3 AIR effectors were identified; instead a cell type-spe...Continue Reading

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Citations

Apr 21, 2017·Nucleic Acids Research·Andrew P HutchinsDuanqing Pei
Feb 22, 2018·Proceedings of the National Academy of Sciences of the United States of America·Huiyuan ZhangStephanie S Watowich
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Jan 8, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaji LiuJeffrey J Saucerman
Jan 20, 2018·Cell Regeneration·Xiuling FuAndrew Paul Hutchins

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Datasets Mentioned

BETA
GSE55385

Methods Mentioned

BETA
flow cytometry
RNA-seq
ChIP-seq
HT-SELEX
lavage
FCS

Software Mentioned

DESeq
ENSEMBL
PSCAN
RSEM
EDASeq
GOSeq
bowtie
WGCNA

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