Relationships Between Eosinophilic Inflammation, Tissue Remodeling, and Fibrosis in Eosinophilic Esophagitis - 12/08/11

Doi : 10.1016/j.iac.2008.10.003

Seema S. Aceves, MD, PhD ^a,^b,^c, Steven J. Ackerman, PhD ^d,^e,^⁎
^a Division of Allergy and Immunology, Rady Children’s Hospital, 3020 Children’s Way, MC 5114, San Diego, CA 92123–6791, USA
^b Department of Pediatrics, Division of Allergy and Immunology, 9500 Gilman Drive, MC-0635, University of California, La Jolla, CA 92093, USA
^c Department of Medicine, Division of Allergy and Immunology, 9500 Gilman Drive, MC-0635, University of California, La Jolla, CA 92093, USA
^d Department of Biochemistry and Molecular Genetics (M/C 669), 900 South Ashland Avenue, Room 2074, Molecular Biology Research Building, The University of Illinois at Chicago College of Medicine, Chicago, IL 60607–7170, USA
^e Department of Medicine, 900 South Ashland Avenue, University of Illinois at Chicago, Chicago, IL 60607-7170, USA

Corresponding author. Department of Biochemistry and Molecular Genetics (M/C 669), 900 South Ashland Avenue, Room 2074, Molecular Biology Research Building, The University of Illinois at Chicago College of Medicine, Chicago, IL 60607.

Abstract

The clinical and pathologic features of eosinophilic esophagitis (EE) include extensive tissue remodeling. Increasing evidence supports a key role for the eosinophil in multiple aspects of the esophageal remodeling and fibrosis seen in this allergic disease. This article reviews the clinical implications of esophageal remodeling and fibrosis in EE and discusses the possible pathogenic mechanisms inducing and regulating these responses. The focus is specifically on eosinophil and cytokine interactions with the esophageal epithelium, vascular endothelium, resident fibroblasts, and smooth muscle. Current and potential therapeutic interventions are discussed that may impact the development or resolution of chronic esophageal remodeling and fibrosis in EE.

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Keywords : Eosinophilic esophagitis, Eosinophils, Inflammation, Remodeling, Fibrosis, Angiogenesis, Transforming growth factor-β

Plan

Clinical implications of tissue remodeling

Epithelial Changes in Relation to Fibrosis

Clinical Implications of Smooth Muscle Hyperplasia

Pathogenic Mechanisms of Eosinophil–Smooth Muscle Interactions

Clinical Implications of Fibrosis

Pathogenic Mechanisms of Eosinophil-Mediated Fibrosis

Clinical Implications of Angiogenesis

Pathogenic mechanisms of eosinophil-induced angiogenesis

Therapeutics and tissue remodeling

Summary

This work was supported by grants from the National Institutes of Health, R21AI079925 (SJA); an American Gastroenterological Association (AGA) Translational Research Award (SJA); an American Partnership for Eosinophilic Diseases (APFED) HOPE Research Award (SSA); an American Academy of Allergy, Asthma, Immunology Junior Women in Allergy grant (SSA); and a gift from the Campaign Urging Research on Eosinophilic Diseases (CURED) (SJA).