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The Immunologic Mechanisms of Eosinophilic Esophagitis

  • Allergens (RK Bush and JA Woodfolk, Section Editors)
  • Published:
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Abstract

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease that is triggered by food and/or environmental allergens and is characterized by a clinical and pathologic phenotype of progressive esophageal dysfunction due to tissue inflammation and fibrosis. EoE is suspected in patients with painful swallowing, among other symptoms, and is diagnosed by the presence of 15 or more eosinophils per high-power field in one or more of at least four esophageal biopsy specimens. The prevalence of EoE is increasing and has now reached rates similar to those of other chronic gastrointestinal disorders such as Crohn’s disease. In recent years, our understanding of the immunologic mechanisms underlying this condition has grown considerably. Thanks to new genetic, molecular, cellular, animal, and translational studies, we can now postulate a detailed pathway by which exposure to allergens results in a complex and coordinated type 2 inflammatory cascade that, if not intervened upon, can result in pain on swallowing, esophageal strictures, and food impaction. Here, we review the most recent research in this field to synthesize and summarize our current understanding of this complex and important disease.

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Abbreviations

EoE:

Eosinophilic esophagitis

Th:

T helper cell

GERD:

Gastroesophageal reflux disease

Ig:

Immunoglobulin

CCL:

C-C motif ligand

TGF-β:

Transforming growth factor beta

TSLP:

Thymic stromal lymphopoietin

IL:

Interleukin

DSG:

Desmosomal cadherin desmoglein

miRNA:

MicroRNA

STAT:

Signal transducer and activator of transcription

CD:

Cluster of differentiation

PARP:

Poly(ADP-ribose) polymerase

TNF-α:

Tumor necrosis factor alpha

PGD:

Prostaglandin

CRTH2:

Chemoattractant receptor expressed on Th2 cells

ILCs:

Innate lymphoid cells

iNKTs:

Invariant natural killer T cells

APC:

Antigen-presenting cell

MHC:

Major histocompatibility complex

HR:

Histamine receptor

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Acknowledgments

DAH is supported by a Resident Research Grant from the American Academy of Pediatrics. JMS is supported by the Stuart Starr Endowed Chair of Pediatrics, The Children’s Hospital of Philadelphia Eosinophilic Esophagitis Fund, a Food Allergy Research & Education, Inc. Clinical Network grant, and the Consortium of Eosinophilic Gastrointestinal Disease Researchers (U54 AI117804) which is part of the Rare Disease Clinical Research Network, an initiative of the National Center for Advancing Translational Sciences (NCATS) Office of Rare Disease Research, and is funded by NCATS and collaborating institute centers.

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  1. Institute for Immunology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    David A. Hill & Jonathan M. Spergel

  2. Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, 3550 Market St., Philadelphia, PA, 19104, USA

    David A. Hill & Jonathan M. Spergel

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Dr. Spergel reports grants from NIH, DBV Technology, Aimmune Therapeutics, FARE Clinical Network, and Stanford Food Allergy Center and is a consultant for Dannone. Dr. Hill reports grants from the AAP. The authors have no financial relationships or other conflicts of interest relevant to this article to disclose.

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Hill, D.A., Spergel, J.M. The Immunologic Mechanisms of Eosinophilic Esophagitis. Curr Allergy Asthma Rep 16, 9 (2016). https://doi.org/10.1007/s11882-015-0592-3

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