Miller Marina, Beppu Andrew, Rosenthal Peter, Pham Alexa, Das Sudipta, Karta Maya, Song Dae Jin, Vuong Christine, Doherty Taylor, Croft Michael, Zuraw Bruce, Zhang Xu, Gao Xiang, Aceves Seema, Chouiali Fazila, Hamid Qutayba, Broide David H
Department of Medicine, University of California, San Diego, La Jolla, CA 92093;
Department of Pediatrics, Korea University College of Medicine, Seoul 02841, Korea;
J Immunol. 2015 Oct 15;195(8):3546-56. doi: 10.4049/jimmunol.1501105. Epub 2015 Sep 9.
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.
慢性哮喘与气道重塑及肺功能下降有关。在本文中，我们发现卵泡抑素样蛋白1（Fstl1），一种此前未与哮喘相关联的介质，在重度哮喘患者的肺部巨噬细胞中高表达。在巨噬细胞/髓系细胞中Fstl1失活的慢性过敏原激发的Lys-Cre(tg)/Fstl1(Δ/Δ)小鼠，其气道重塑显著减轻，抑瘤素M（OSM）水平降低，OSM是一种此前未知受Fstl1调控的细胞因子。在小鼠研究中证实了Fstl1诱导OSM对气道重塑的重要性，在这些研究中，给予Fstl1可诱导气道重塑并增加OSM，而给予抗OSM抗体则可阻断Fstl1对诱导气道重塑、嗜酸性气道炎症和气道高反应性的作用，这些都是哮喘的主要特征。总体而言，这些研究表明Fstl1/OSM途径可能是抑制重度人类哮喘气道重塑的新途径。
