Genomics

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Chromatin Remodeling Drives Immune-Fibroblast Cell Communication in Heart Failure (ChIP-Seq)


ABSTRACT: Chronic inflammation and tissue fibrosis are common stress responses that worsen organ function, yet their crosstalk is poorly understood. Here, we show that conditional deletion of the transcription co-activator Brd4 in Cx3cr1-positive myeloid cells ameliorates heart failure and is associated with a dramatic reduction in fibroblast activation. We identified a specific BRD4-occupied enhancer in Cx3cr1-positive cells that controls expression of Interleukin-1 beta (Il1b), and show that secreted IL1B activates a p65/RELA-dependent enhancer downstream of MEOX1, driving a profibrotic response in human cardiac fibroblasts. In vivo, antibody-mediated IL1B neutralization prevented stress-induced expression of MEOX1, inhibited fibroblast activation, and improved cardiac function in heart failure. The elucidation of BRD4-dependent crosstalk between a specific immune cell subset and fibroblasts through IL1B provides new therapeutic strategies for heart disease and other disorders of chronic inflammation and maladaptive tissue remodeling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221694 | GEO | 2024/07/03

REPOSITORIES: GEO

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