IL-11 is a therapeutic target in idiopathic pulmonary fibrosis

Cook, S.; Ng, B.; Dong, J.; Viswanathan, S.; DAgostino, G.; Widjaja, A.; Lim, W.-W.; Ko, N.; Tan, J.; Chothani, S.; Huang, B.; Xie, C.; Chacko, A.-M.; Guimaraes-Camboa, N.; Evans, S.; Byrne, A.; Maher, T.; Liang, J.; Noble, P.; Schafer, S.

doi:10.1101/336537

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bioRxiv · 10.1101/336537

IL-11 is a therapeutic target in idiopathic pulmonary fibrosis

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Abstract

Idiopathic pulmonary fibrosis (IPF) remains a progressive disease despite best medical management. We previously identified IL-11 as a critical factor for cardiovascular fibrosis and examine here its role in pulmonary fibrosis. IL-11 is consistently upregulated in IPF genomic datasets, which we confirmed by histology. Pulmonary fibroblasts stimulated with IL-11 transform into invasive myofibroblasts whereas fibroblasts from Il11ra deleted mice did not respond to pro-fibrotic stimuli. In the mouse, injection of recombinant Il-11 or fibroblast-specific expression of Il-11 caused pulmonary fibrosis. We then generated a neutralising IL-11 binding antibody that blocks lung fibroblast activation across species. In a mouse model of IPF, anti-IL-11 therapy attenuated lung fibrosis and specifically blocked Erk activation. These data prioritise IL-11 as an accessible drug target in IPF.\n\nOne Sentence SummaryNon-canonical IL-11 signalling is a central hallmark of idiopathic pulmonary fibrosis and represents a novel target for antibody therapies.

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Cook, S., Ng, B., Dong, J., Viswanathan, S., DAgostino, G., Widjaja, A., Lim, W.-W., Ko, N., Tan, J., Chothani, S., Huang, B., Xie, C., Chacko, A.-M., Guimaraes-Camboa, N., Evans, S., Byrne, A., Maher, T., Liang, J., Noble, P., Schafer, S.. 2018-06-02. IL-11 is a therapeutic target in idiopathic pulmonary fibrosis. https://doi.org/10.1101/336537

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