Journal
BLOOD
Volume 119, Issue 13, Pages E110-E119Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-09-381483
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Funding
- Japan Society for the Promotion of Science (JSPS)
- Kishimoto Foundation
- ETHZ-JST
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Inflammation is a powerful response of the immune system against invading pathogens, and must be cancelled when unneeded or otherwise death inevitably follows. In macrophages, the anti-inflammatory response (AIR) is driven by STAT3 upon IL-10 signaling. The role of STAT3 is to stimulate the expression of specific genes that in-turn suppress the transcription of proinflammatory genes. Here we describe a systematic approach to identify the elusive STAT3-controlled effectors of the AIR. In vivo STAT3-binding sites were identified by ChIP-seq, coupled to expression analysis by RNA-seq, both in resting and IL-10-treated peritoneal macrophages. We report the genomic targets of STAT3 and show that STAT3's transcriptional program during the AIR is highly specific to IL-10-stimulated macrophages, that STAT3 is a positive transcriptional regulator, and we predict several putative AIR factors that merit further investigation. This is the first in-depth study of the AIR by next-generation sequencing and provides an unprecedented degree of detail into this fundamental physiologic response. (Blood. 2012;119(13):e110-e119)
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