Fstl1 Promotes Asthmatic Airway Remodeling by Inducing Oncostatin M

Marina Miller, Andrew Beppu, Peter Rosenthal, Alexa Pham, Sudipta Das, Maya Karta, Dae J.in Song, Christine Vuong, Taylor Doherty, Michael Croft, Bruce Zuraw, Xu Zhang, Xiang Gao, Seema Aceves, Fazila Chouiali, Qutayba Hamid, David H. Broide

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Chronic asthma is associated with airway remodeling and decline in lung function. In this article, we show that follistatin-like 1 (Fstl1), a mediator not previously associated with asthma, is highly expressed by macrophages in the lungs of humans with severe asthma. Chronic allergen-challenged Lys-Cre(tg) /Fstl1(Δ/Δ) mice in whom Fstl1 is inactivated in macrophages/myeloid cells had significantly reduced airway remodeling and reduced levels of oncostatin M (OSM), a cytokine previously not known to be regulated by Fstl1. The importance of the Fstl1 induction of OSM to airway remodeling was demonstrated in murine studies in which administration of Fstl1 induced airway remodeling and increased OSM, whereas administration of an anti-OSM Ab blocked the effect of Fstl1 on inducing airway remodeling, eosinophilic airway inflammation, and airway hyperresponsiveness, all cardinal features of asthma. Overall, these studies demonstrate that the Fstl1/OSM pathway may be a novel pathway to inhibit airway remodeling in severe human asthma.

Original languageEnglish
Pages (from-to)3546-3556
Number of pages11
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume195
Issue number8
DOIs
Publication statusPublished - 2015 Oct 15

ASJC Scopus subject areas

  • Immunology

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    Miller, M., Beppu, A., Rosenthal, P., Pham, A., Das, S., Karta, M., Song, D. J. I., Vuong, C., Doherty, T., Croft, M., Zuraw, B., Zhang, X., Gao, X., Aceves, S., Chouiali, F., Hamid, Q., & Broide, D. H. (2015). Fstl1 Promotes Asthmatic Airway Remodeling by Inducing Oncostatin M. Journal of immunology (Baltimore, Md. : 1950), 195(8), 3546-3556. https://doi.org/10.4049/jimmunol.1501105