title: Transforming growth factor β and severe asthma: a perfect storm.
abstract: Asthma is a chronic inflammatory airway disease involving complex interplay between resident and infiltrative cells, which in turn are regulated by a wide range of host mediators. Identifying useful biomarkers correlating with clinical symptoms and degree of airway obstruction remain important to effective future asthma treatments. Transforming growth factor β (TGF-β) is a major mediator involved in pro-inflammatory responses and fibrotic tissue remodeling within the asthmatic lung. Its role however, as a therapeutic target remains controversial. The aim of this review is to highlight its role in severe asthma including interactions with adaptive T-helper cells, cytokines and differentiation through regulatory T-cells. Associations between TGF-β and eosinophils will be addressed and the effects of genetic polymorphisms of the TGF-β1 gene explored in the context of asthma. We highlight TGF-β1 as a potential future therapeutic target in severe asthma including its importance in identifying emerging clinical phenotypes in asthmatic subjects who may be suitable for individualized therapy through TGF-β modulation.
authors.affiliation: Department of Respiratory Medicine, Mater Misericordiae Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: Mazen
authors.initials: M
authors.lastname: Al-Alawi
authors.affiliation: Department of Respiratory Medicine, Mater Misericordiae Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: Tidi
authors.initials: T
authors.lastname: Hassan
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. Electronic address: schotirmall@ntu.edu.sg.
authors.forename: Sanjay H
authors.initials: SH
authors.lastname: Chotirmall
mesh_terms: D001249:Asthma / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1
keywords: Asthma; Eosinophil; TGF-β; Target; Therapy