The Role of Mast Cells in Aspirin-Exacerbated Respiratory Disease (AERD) Pathogenesis: Implications for Future Therapeutics

• Type of Material: Article
• Authors: Merin E. Kuruvilla, Emory University; Kristine Vanijcharoenkarn, Emory University; Joshua Levy, Emory University
• Language: English
• Date: 2020-10-12
• Publisher: Dove Medical Press
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Kuruvilla et al.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2147/JAA.S237463
• Title of Journal or Parent Work: Journal of Asthma and Allergy
• Volume: 13
• Start Page: 463
• End Page: 470
• Grant/Funding Information: Dr. Levy is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR002378 and KL2TR002381. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: aspirin-exacerbated respiratory disease; mast cells; humanized monoclonal antibody; asthma; drug sensitivity
• Research Categories: Health Sciences, Pharmacology

Abstract

Mast cells (MC) have recently been demonstrated to play an integral role in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). When activated, MCs release pre-formed granules of many pro-inflammatory mediators, including histamine, serotonin, and various chemokines and cytokines including tumor necrosis factor (TNF)-α, interferon ɣ (IFN ɣ), macrophage inhibitory factor, transforming growth factor, interleukin (IL) 1, 3–6, 9, 10, 13 and 16. These mediators promote inflammation in AERD by recruiting or activating a network of cells involved in acute and chronic inflammatory pathways, such as endothelial, epithelial, stromal, and other immune cells. Several studies have implicated multifactorial pathways for MC activation in AERD beyond classical IgE mediated mechanisms. The elucidation of these complex networks therefore represents important targets for innovative patient therapeutics. This review summarizes classic and alternative pathways of MC activation in AERD with a special focus in relation to new and emerging treatment strategies.