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IL-11 is a therapeutic target in idiopathic pulmonary fibrosis

ABSTRACT: IL-11 is a therapeutic target in idiopathic pulmonary fibrosis

PROVIDER: PRJNA542170 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9036850_1.fastq.gz	Fastqsanger.gz
	SRR9036850_2.fastq.gz	Fastqsanger.gz
	SRR9036860_1.fastq.gz	Fastqsanger.gz
	SRR9036860_2.fastq.gz	Fastqsanger.gz
	SRR9036870_1.fastq.gz	Fastqsanger.gz

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IL-11 is a therapeutic target in idiopathic pulmonary fibrosis

Project description:Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease where invasive pulmonary myofibroblasts secrete collagen and destroy lung integrity. Here we show that IL-11 is upregulated in the lung of IPF patients, associated with disease severity and is secreted from IPF fibroblasts. In vitro, IL-11 stimulates lung fibroblasts to become invasive, ACTA2+ve, collagen secreting myofibroblasts, in an ERK-dependent fashion. In mice, fibroblast-specific transgenic expression or administration of Il-11 drives lung fibroblast-to-myofibroblast transformation and causes lung fibrosis. Il11ra1 deleted mice, whose lung fibroblasts are unresponsive to pro-fibrotic stimulation, are protected from fibrosis in the bleomycin mouse model of pulmonary fibrosis. We generated an IL-11 neutralising antibody that blocks lung fibroblast activation downstream of multiple stimuli and reverses myofibroblast activation. In therapeutic studies, anti-IL-11 treatment both prevented and reversed lung fibrosis, which was accompanied by diminished Erk activation. These data prioritise IL-11 as a drug target for lung fibrosis and IPF.

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