Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis

Abstract Loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and incompletely penetrant craniosynostosis. The impact of LOF in IL11 has not been characterized. We generated IL11 knockout (Il11 −/−) mice that are born in expected ratios and have n...

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Autores principales:	Benjamin Ng, Anissa A. Widjaja, Sivakumar Viswanathan, Jinrui Dong, Sonia P. Chothani, Stella Lim, Shamini G. Shekeran, Jessie Tan, Narelle E. McGregor, Emma C. Walker, Natalie A. Sims, Sebastian Schafer, Stuart A. Cook
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d5124096b01d4998921d03195394e3df
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spelling	oai:doaj.org-article:d5124096b01d4998921d03195394e3df2021-12-02T18:34:20ZSimilarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis10.1038/s41598-021-93623-92045-2322https://doaj.org/article/d5124096b01d4998921d03195394e3df2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93623-9https://doaj.org/toc/2045-2322Abstract Loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and incompletely penetrant craniosynostosis. The impact of LOF in IL11 has not been characterized. We generated IL11 knockout (Il11 −/−) mice that are born in expected ratios and have normal hematological profiles. Lung fibroblasts from Il11 −/− mice are resistant to pro-fibrotic stimulation with TGFβ1. Following bleomycin-induced lung injury, Il11 −/− mice are protected from pulmonary fibrosis and exhibit lesser ERK, STAT3 and NF-kB activation, reduced Il1b, Timp1, Ccl2 and diminished IL6 expression, both at baseline and after injury: placing Il11 activity upstream of IL6 in this model. Il11 −/− female mice are infertile. Unlike Il11ra1 −/− mice, Il11 −/− mice do not have craniosynostosis, have normal long bone mass and reduced body weights. These data further establish the role of IL11 signaling in lung fibrosis while suggesting that bone development abnormalities can be associated with mutation of IL11RA but not IL11, which may have implications for therapeutic targeting of IL11 signaling.Benjamin NgAnissa A. WidjajaSivakumar ViswanathanJinrui DongSonia P. ChothaniStella LimShamini G. ShekeranJessie TanNarelle E. McGregorEmma C. WalkerNatalie A. SimsSebastian SchaferStuart A. CookNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin Ng Anissa A. Widjaja Sivakumar Viswanathan Jinrui Dong Sonia P. Chothani Stella Lim Shamini G. Shekeran Jessie Tan Narelle E. McGregor Emma C. Walker Natalie A. Sims Sebastian Schafer Stuart A. Cook Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis
description	Abstract Loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and incompletely penetrant craniosynostosis. The impact of LOF in IL11 has not been characterized. We generated IL11 knockout (Il11 −/−) mice that are born in expected ratios and have normal hematological profiles. Lung fibroblasts from Il11 −/− mice are resistant to pro-fibrotic stimulation with TGFβ1. Following bleomycin-induced lung injury, Il11 −/− mice are protected from pulmonary fibrosis and exhibit lesser ERK, STAT3 and NF-kB activation, reduced Il1b, Timp1, Ccl2 and diminished IL6 expression, both at baseline and after injury: placing Il11 activity upstream of IL6 in this model. Il11 −/− female mice are infertile. Unlike Il11ra1 −/− mice, Il11 −/− mice do not have craniosynostosis, have normal long bone mass and reduced body weights. These data further establish the role of IL11 signaling in lung fibrosis while suggesting that bone development abnormalities can be associated with mutation of IL11RA but not IL11, which may have implications for therapeutic targeting of IL11 signaling.
format	article
author	Benjamin Ng Anissa A. Widjaja Sivakumar Viswanathan Jinrui Dong Sonia P. Chothani Stella Lim Shamini G. Shekeran Jessie Tan Narelle E. McGregor Emma C. Walker Natalie A. Sims Sebastian Schafer Stuart A. Cook
author_facet	Benjamin Ng Anissa A. Widjaja Sivakumar Viswanathan Jinrui Dong Sonia P. Chothani Stella Lim Shamini G. Shekeran Jessie Tan Narelle E. McGregor Emma C. Walker Natalie A. Sims Sebastian Schafer Stuart A. Cook
author_sort	Benjamin Ng
title	Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis
title_short	Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis
title_full	Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis
title_fullStr	Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis
title_full_unstemmed	Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis
title_sort	similarities and differences between il11 and il11ra1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d5124096b01d4998921d03195394e3df
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Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis

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