Djoke van Gosliga

Protocadherin-1 deficiency increases baseline and allergen-induced airway hyperresponsiveness in mice

Bao-Han Ly, Uilke Brouwer, Laura Hesse, Kuldeep Kumawat et autres

Asthma is a heterogeneous airway disease characterized by chronic inflammation, airway hyperresponsiveness (AHR), and airway remodeling. Previously, we identified Protocadherin-1 (PCDH1) as a susceptibility gene for AHR, a hallmark of asthma. PCDH1 is an adhesion molecule, highly expressed in the airway epithelium. …

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Dynamics of nasal transcriptomics during step-up treatment in children with uncontrolled asthma

Yidan Sun, Elise M. A. Slob, Lieke C. E. Noij, Tatiana Karp et autres

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Protocadherin-1 loss in human primary airway epithelial cells induces hillock-squamous cell differentiation

Bao-Han Ly, Djoke van Gosliga, Georgia N. Ithakisiou, Gimano D. Amatngalim et autres

PCDH1 is a susceptibility gene for airway hyperresponsiveness, a hallmark of asthma. PCDH1 is highly expressed in the airway epithelium, localized to cell-cell contact sites. Previous analysis of Pcdh1-KO mice suggested enrichment of hillock-squamous differentiation in the airways of those mice. However, …

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Single-cell characterization of loss of mouse Protocadherin-1, a gene for airway hyperresponsiveness

Bao-Han Ly, Uilke Brouwer, Laura E. Hesse, Arjen H. Petersen et autres

Asthma is a heterogeneous airway disease. We previously identified PCDH1 as a susceptibility gene for airway hyperresponsiveness (AHR), a hallmark of asthma. PCDH1 is an adhesion molecule, highly expressed in the airway epithelium. However, its role in AHR, airway inflammation, and remodeling …

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The airway epithelium in patients with asthma is in a continuous state of repair

Tessa E. Gillett, Aurore C. A. Gay, Martin Banchero, Marijn Berg et autres

The airway epithelium is altered in patients with asthma, with reduced barrier function and goblet cell metaplasia. Recently, single cell RNA-seq has identified 15+ distinct airway epithelial cell types in the Human Lung Cell Atlas, but it is unknown whether these newly …

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IL-13 results in short term epithelial dedifferentation and long term goblet cell expansion in PBECs from patients with asthma

Jelmer Vlasma, Aurore C. A. Gay, Martin Banchero, Judith M. Vonk et autres

Introduction: Asthma is a heterogeneous lung disease, characterized by remodeled airways and mucus hypersecretion. Previously, we showed that the airway composition is changed in patients with asthma, showing more mucus-producing cells such as goblet and mucous ciliated cells compared to healthy controls. …

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Airway epithelial cell response to RSV is mostly impaired in goblet and multiciliated cells in asthma

Aurore C. A. Gay, Martin Banchero, Orestes A. Carpaij, Tessa Kole et autres

Background In patients with asthma, respiratory syncytial virus (RSV) infections can cause disease exacerbation by infecting the epithelial layer of the airways, inducing subsequent immune response. The type I interferon antiviral response of epithelial cells upon RSV infection is found to be …

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An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma

Zaid W. Elhusseini, Dmitry Khalenkow, Andy Lan, Thys van der Molen et autres

BACKGROUND: Asthma is stratified into type 2-high and type 2-low inflammatory phenotypes. Limited success has been achieved in developing drugs that target type 2-low inflammation. Previous studies have linked IL-6 signaling to severe asthma. IL-6 cooperates with soluble-IL-6Rα to activate cell signaling …

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Single-cell RNA sequencing reveals defective bronchial epithelial cell differentiation in patients with severe COPD in 3-dimensional organoid cultures

Kingsley Okechukwu Nwozor, Tillie‐Louise Hackett, Chen Xi Yang, Aurore C. A. Gay et autres

Background: Impaired airway epithelial barrier function and repair are thought to be key drivers in chronic obstructive pulmonary disease (COPD) pathology, however, the mechanisms involved remain not fully understood. Objective: Assess bronchial epithelial cell differentiation in an organoid model by COPD severity …

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SIL-6Rα amplified IL-6 signaling in bronchial epithelial cells defines a subgroup of asthma patients low in sputum eosinophils

Zaid W. Elhusseini, Dmitry Khalenkow, Andy Lan, Maarten van den Berge et autres

Background: Asthma is clinically stratified into type 2-high and type 2-low asthma. Limited success has been achieved in developing drugs that target type-2 low inflammation. Previous studies have linked IL-6 signaling to type 2-low asthma. Objective: We sought to study the role …

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Airway epithelial response to RSV is impaired in multiciliated and goblet cells in asthma

Aurore C. A. Gay, Martin Banchero, Orestes A. Carpaij, Tessa Kole et autres

Abstract In patients with asthma, respiratory syncytial virus (RSV) infections can cause disease exacerbations by infecting the epithelial layer of the airways, inducing an innate and adaptive immune response. The type-I interferon antiviral response of epithelial cells upon RSV infection is found …

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Transcriptional response to RSV in asthma primary bronchial epithelial cells: are the basal cells responsible for the reduced NF-kB response?

Aurore C. A. Gay, Marijn Berg, Orestes A. Carpaij, Uilke Brouwer et autres

Rationale: Respiratory syncytial virus (RSV) infection can cause asthma exacerbations. Most - but not all - studies showed that the type-I interferon dependent antiviral response induced by the epithelial cells after RSV infection is reduced in asthma. The molecular mechanisms responsible for …

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