Fibrostenotic eosinophilic esophagitis might reflect epithelial lysyl oxidase induction by fibroblast-derived TNF-α

Abstract

(to K.A.W. and H.N.). J.M.S. is funded by the Stuart Starr Endowed Chair, Food Allergy Research and Education. J.M.S. and A.B.M. are funded in part by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). CEGIR (U54 AI117804) is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between the National Institute of Allergy and Infectious Diseases (NIAID), NIDDK, and NCATS. CEGIR is also supported by patient advocacy groups, including APFED, CURED, and EFC. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

“…Major cytokines involved in the pathogenesis of eosinophilic esophagitis such as IL‐4, IL‐5, IL‐13, and TNF have been tested for the treatment of eosinophilic esophagitits 133 . Along with Th2 cytokines, TGF‐β is the major cytokine that mediates lamina propria remodeling in eosinophilic esophagitis 134 . Recently, it has been reported that TGF‐β alters esophageal epithelial barrier function via claudin‐7 135 .…”

Modeling Epithelial Homeostasis and Reactive Epithelial Changes in Human and Murine Three‐Dimensional Esophageal Organoids

“…Here we provide an example of such an experiment by treating normal esophageal organoids with interleukin 13 (IL-13) to model reactive changes induced in esophageal epithelium by eosinophils; however, any bioactive compounds (cytokines, antibodies, small molecule inhibitors) can be utilized to model pathologic conditions and/or treatment strategies. Representative images of esophageal organoids treated with IL-13, as well as gene expression profiles of select EoE-relevant genes (Blanchard et al, 2007;Kasagi et al, 2019), can be found in Figure 2.…”

Bagels and LOX in patients with eosinophilic esophagitis

“…In this issue of the Journal, Kasagi et al 8 provide evidence that the enzyme lysyl oxidase (LOC, protein product of LOX), which promotes formation of extracellular collagen fibers, can serve as a biomarker for fibrostenotic disease in patients with EoE. Previous publications revealed that LOX expression was upregulated in biopsy specimens from patients with EoE and in an epithelial cell line.…”

“…Previous publications revealed that LOX expression was upregulated in biopsy specimens from patients with EoE and in an epithelial cell line. 9,10 Kasagi et al 8 found that LOX expression correlated with clinical and endoscopic fibrostenotic disease. This upregulation was linked to epithelial cells stimulated by TNF-a produced by fibroblasts.…”

“…The work presented in the study by Kasagi et al 8 focuses on the need for better diagnostic methods to evaluate fibrostenotic EoE. Currently, the gold standard for a diagnosis of fibrostenosis is based on evaluation of the lamina propria from patients' biopsy specimens.…”