Abstract

Chronic eosinophilic inflammation is associated with tissue remodeling and fibrosis in a number of chronic T-helper 2 (Th2)-mediated diseases including eosinophilic esophagitis (EoE) and asthma. Chronic inflammation results in dysregulated tissue healing, leading to fibrosis and end organ dysfunction, manifesting clinically as irreversible airway obstruction in asthma and as esophageal rigidity, strictures, narrowing, dysmotility, dysphagia, and food impactions in EoE. Current therapies for EoE and asthma center on reducing inflammation-driven tissue remodeling and fibrosis with corticosteroids, coupled with symptomatic control and allergen avoidance. Additional control of Th2 inflammation can be achieved in select asthma patients with biologic therapies such as anti-IL-5 and anti-IL-13 antibodies, which have also been trialed in EoE. Recent molecular analysis suggests an emerging role for structural cell dysfunction, either inherited or acquired, in the pathogenesis and progression of EoE and asthma tissue remodeling. In addition, new data suggest that inflammation-independent end organ rigidity can alter structural cell function. Herein, we review emerging data and concepts for the pathogenesis of tissue remodeling and fibrosis primarily in EoE and relevant pathogenetic parallels in asthma, focusing additionally on emerging disease-specific therapies and the ability of these therapies to reduce tissue remodeling in subsets of patients.

Highlights

  • Allergic inflammation has the capacity to recruit eosinophils to the site of inciting stimulus

  • Chronic, unbridled inflammation in eosinophilic esophagitis (EoE) leads to progressive esophageal fibrostenosis with rigidity and dysmotility with food impactions [6,7,8,9]

  • IL-13 has emerged as a master regulator in EoE and drives the recruitment and activation of eosinophils via eotaxin-3/CCL26 and IL-5, further augmenting T-helper 2 (Th2) inflammation in the esophagus that can result in irreversible stricture formation [42, 47, 48]

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Summary

Tissue Remodeling in Chronic Eosinophilic Esophageal

Inflammation: Parallels in Asthma and Therapeutic Perspectives. Front. Chronic eosinophilic inflammation is associated with tissue remodeling and fibrosis in a number of chronic T-helper 2 (Th2)-mediated diseases including eosinophilic esophagitis (EoE) and asthma. Current therapies for EoE and asthma center on reducing inflammation-driven tissue remodeling and fibrosis with corticosteroids, coupled with symptomatic control and allergen avoidance. Recent molecular analysis suggests an emerging role for structural cell dysfunction, either inherited or acquired, in the pathogenesis and progression of EoE and asthma tissue remodeling. We review emerging data and concepts for the pathogenesis of tissue remodeling and fibrosis primarily in EoE and relevant pathogenetic parallels in asthma, focusing on emerging disease-specific therapies and the ability of these therapies to reduce tissue remodeling in subsets of patients

INTRODUCTION
CLINICAL FEATURES OF TISSUE
Histologic Features of Remodeling
Interleukins and Cytokines Involved in Remodeling
Tissue mastocytosis Structural cell alterations
Eosinophils and Other Immune Cells in Tissue Remodeling
Profibrotic Cytokines
Mechanotransduction and Remodeling
CURRENT AND EMERGING THERAPEUTICS FOR ALLERGIC REMODELING
Topical Corticosteroids
Elimination Diets in EoE
Biologic Therapy
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