Mast cells disrupt the function of the esophageal epithelial barrier
Kleuskens, Mirelle T.A.; Bek, Marie K.; Al Halabi, Youmna; Blokhuis, Bart R.J.; Diks, Mara A.P.; Haasnoot, Maria L.; Garssen, Johan; Bredenoord, Albert J.; van Esch, Betty C.A.M.; Redegeld, Frank A.
(2023) Mucosal Immunology, volume 16, issue 5, pp. 567 - 577
(Article)
Abstract
Mast cells (MCs) accumulate in the epithelium of patients with eosinophilic esophagitis (EoE), an inflammatory disorder characterized by extensive esophageal eosinophilic infiltration. Esophageal barrier dysfunction plays an important role in the pathophysiology of EoE. We hypothesized that MCs contribute to the observed impaired esophageal epithelial barrier. Herein, we demonstrate that
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coculture of differentiated esophageal epithelial cells with immunoglobulin E-activated MCs significanly decreased epithelial resistance by 30% and increased permeability by 22% compared with non-activated MCs. These changes were associated with decreased messenger RNA expression of barrier proteins filaggrin, desmoglein-1 and involucrin, and antiprotease serine peptidase inhibitor kazal type 7. Using targeted proteomics, we detected various cytokines in coculture supernatants, most notably granulocyte-macrophage colony-stimulating factor and oncostatin M (OSM). OSM expression was increased by 12-fold in active EoE and associated with MC marker genes. Furthermore, OSM receptor-expressing esophageal epithelial cells were found in the esophageal tissue of patients with EoE, suggesting that the epithelial cells may respond to OSM. Stimulation of esophageal epithelial cells with OSM resulted in a dose-dependent decrease in barrier function and expression of filaggrin and desmoglein-1 and an increase in protease calpain-14. Taken together, these data suggest a role for MCs in decreasing esophageal epithelial barrier function in EoE, which may in part be mediated by OSM.
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Keywords: Eosinophilic esophagitis, Epithelial barrier, IgE, Mast cell, Oncostatin M, Immunology and Allergy, Immunology
ISSN: 1933-0219
Publisher: Nature Publishing Group
Note: Funding Information: AJB received research funding from Norgine, Thelial, and SST, and received speaker and/or consulting fees from Laborie, Arena, EsoCap, Medtronic, Dr. Falk Pharma, Calypso Biotech, Alimentiv, Sanofi, Reckett, Regeneron, and AstraZeneca (all unrelated to this work). JG and BCAMVE are partly employed by Danone Nutricia Research. All other authors report no conflicts of interest. Funding Information: This research is funded within the Partnership between the Dutch Research Council (NWO) domain Applied and Engineered Sciences, and Danone Nutricia Research, with additional financial support from Topsector Agri and Food: project number 16495 with the acronym LOIRE. AJB is supported by Vidi grant 91718300 from NWO. Publisher Copyright: © 2023 The Author(s)
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