CITED2 limits pathogenic inflammatory gene programs in myeloid cells.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Hang Pong NgGanapati H Mahabeleshwar

Abstract

Monocyte-derived macrophages are the major innate immune cells that provide the first line of cellular defense against infections or injuries. These recruited macrophages at the site of inflammation are exposed to a broad range of cytokines that categorically incite a robust pro-inflammatory response. However, macrophage pro-inflammatory activation must be under exquisite control to avert unbridled inflammation. Thus, endogenous mechanisms must exist that rigorously preserve macrophage quiescence and yet, allow nimble pro-inflammatory macrophage response with precise spatiotemporal control. Herein, we identify the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) as a critical intrinsic negative regulator of inflammation, which broadly attenuates pro-inflammatory gene programs in macrophages. Our in vivo studies revealed that myeloid-CITED2 deficiency significantly heightened macrophages and neutrophils recruitment to the site of inflammation. Our integrated transcriptomics and gene set enrichment analysis (GSEA) studies uncovered that CITED2 deficiency broadly enhances NFκB targets, IFNγ/IFNα responses, and inflammatory response gene expression in macrophages. Using c...Continue Reading

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Citations

Jan 8, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Nour W Al Haj BaddarS Randal Voss
Aug 9, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Atif ZafarGanapati H Mahabeleshwar

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Datasets Mentioned

BETA
GSE147943

Methods Mentioned

BETA
immunoprecipitation
bronchoalveolar lavage
lavages
RNAseq
PCR
transfection
immunoprecipitations
ChIP
bronchoalveolar lavages
bronchoalveolar

Software Mentioned

Image J
Cuffdiff
GENCODE
STAR Aligner
GSEA
Gene Set Enrichment Analysis ( GSEA )
ImageJ
GenePattern

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