Foxa3 Induces Goblet Cell Metaplasia and Inhibits Innate Antiviral Immunity

Gang Chen; Thomas R. Korfhagen; Christopher L. Karp; Soren Impey; Yan Xu; Scott H. Randell; Joseph A. Kitzmiller; Yutaka Maeda; Hans Michael Haitchi; Anusha Sridharan; Albert P. Senft; Jeffrey A. Whitsett

doi:10.1164/rccm.201306-1181oc

February 1, 2014American Journal of Respiratory and Critical Care MedicineOpen Access

Foxa3 Induces Goblet Cell Metaplasia and Inhibits Innate Antiviral Immunity

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Key Points

To identify the role of transcription factor FOXA3 in regulating airway goblet cell metaplasia and innate antiviral immunity in chronic lung diseases.
Analyzed airway tissue samples for FOXA3 expression from patients with asthma and chronic obstructive pulmonary disease.
Engineered transgenic mouse models conditionally expressing Foxa3 in airway epithelial cells and cultured Foxa3-expressing human bronchial epithelial cells.
Identified FOXA3 target genes and signaling pathways using immunostaining, Western blotting, RNA sequencing, and chromatin immunoprecipitation sequencing.
FOXA3 was strongly upregulated in airway goblet cells from patients with asthma and COPD, and was inducible by IL-13 and rhinovirus exposure.
FOXA3 directly induced goblet cell metaplasia and activated gene networks responsible for mucus production and secretion.
FOXA3 impaired rhinovirus clearance by repressing interferon production, IRF-3 phosphorylation, and IKKε expression, alongside key antiviral pattern-recognition receptors including MDA5, RIG-I, and TLR3.

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Implication

Experimental study reveals FOXA3 promotes goblet cell metaplasia and suppresses antiviral interferon signaling in airway cells, indicating a cause for viral vulnerability in chronic lung disease.

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Cite This Study

Chen et al. (2014) studied this question.

synapsesocial.com/papers/6a7d64f2a88f8d6a78a0115d https://doi.org/10.1164/rccm.201306-1181oc

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Foxa3 Induces Goblet Cell Metaplasia and Inhibits Innate Antiviral Immunity

Key Points

No abstract yet

Implication

Discussion

Cite This Study

Foxa3 Induces Goblet Cell Metaplasia and Inhibits Innate Antiviral Immunity

Key Points

No abstract yet

Implication

Discussion

Cite This Study

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