Publication date: Available online 21 May 2019
Source: Journal of Allergy and Clinical Immunology
Author(s): Aiko Saku, Koichi Hirose, Takashi Ito, Arifumi Iwata, Takashi Sato, Hiroyuki Kaji, Tomohiro Tamachi, Akira Suto, Yoshiyuki Goto, Steven E. Domino, Hisashi Narimatsu, Hiroshi Kiyono, Hiroshi Nakajima
Abstract
Graphical abstract
Background
One of the pathognomonic features of asthma is epithelial hyperproduction of mucus which is composed of a series of glycoproteins; however, it remains unclear how glycosylation is induced in asthmatic lung epithelial cells and how glycan residues play a role in the pathogenesis of asthma.
Objective
The objective of this study is to explore comprehensive epithelial glycosylation status induced by allergic inflammation and reveal its possible role in the pathogenesis of asthma.
Methods
We evaluated the glycosylation status of lung epithelium by lectin microarray. We next searched for molecular mechanisms underlying the epithelial glycosylation. We also examined whether the epithelial glycosylation is involved in the induction of allergic inflammation.
Results
Upon allergen inhalation, lung epithelial cells were heavily α(1,2)fucosylated by fucosyltransferase 2 (Fut2), which was induced by the IL-13-Stat6 pathway. Importantly, Fut2-deficient mice (Fut2-/- mice), which lacked lung epithelial fucosylation, exhibited significantly attenuated eosinophilic inflammation and airway hyperresponsiveness in house dust mite (HDM)-induced asthma models. Proteome analyses and immunostaining of the HDM-challenged lung identified that a complement C3 was accumulated in fucosylatied areas. Indeed, Fut2-/- mice showed significantly reduced levels of C3a and impaired accumulation of C3a receptor-expressing monocyte-derived dendritic cells (Mo-DCs) in the lung upon HDM challenge.
Conclusion
Fut2 induces epithelial fucosylation and exacerbates airway inflammation in asthma in part via C3a production and Mo-DC accumulation in the lung.
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