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The enigmatic role of the neutrophil in asthma: Friend, foe or indifferent?

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Title: The enigmatic role of the neutrophil in asthma: Friend, foe or indifferent?
Authors: Snelgrove, RJ
Patel, DF
Patel, T
Lloyd, CM
Item Type: Journal Article
Abstract: Whilst severe asthma has classically been categorized as a predominantly Th2-driven pathology, there has in recent years been a paradigm shift with the realization that it is a heterogeneous disease that may manifest with quite disparate underlying inflammatory and remodelling profiles. A subset of asthmatics, particularly those with a severe, corticosteroid refractory disease, present with a prominent neutrophilic component. Given the potential of neutrophils to impart extensive tissue damage and promote inflammation, it has been anticipated that these cells are closely implicated in the underlying pathophysiology of severe asthma. However, uncertainty persists as to why the neutrophil is present in the asthmatic lung and what precisely it is doing there, with evidence supporting its role as a protagonist of pathology being primarily circumstantial. Furthermore, our view of the neutrophil as a primitive, indiscriminate killer has evolved with the realization that neutrophils can exhibit a marked anti-inflammatory, pro-resolving and wound healing capacity. We suggest that the neutrophil likely exhibits pleiotropic and potentially conflicting roles in defining asthma pathophysiology-some almost certainly detrimental and some potentially beneficial-with context, timing and location all critical confounders. Accordingly, indiscriminate blockade of neutrophils with a broad sword approach is unlikely to be the answer, but rather we should first seek to understand their complex and multifaceted roles in the disease state and then target them with the same subtleties and specificity that they themselves exhibit.
Issue Date: 1-Oct-2018
Date of Acceptance: 11-Jun-2018
URI: http://hdl.handle.net/10044/1/62871
DOI: https://dx.doi.org/10.1111/cea.13191
ISSN: 0954-7894
Publisher: Wiley
Start Page: 1275
End Page: 1285
Journal / Book Title: Clinical and Experimental Allergy
Volume: 48
Issue: 10
Copyright Statement: © 2018 John Wiley & Sons Ltd. This is the pre-peer reviewed version of the following article, which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1111/cea.13191
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Funder's Grant Number: 107059/Z/15/Z
Keywords: 1107 Immunology
1117 Public Health And Health Services
Publication Status: Published
Conference Place: England
Online Publication Date: 2018-06-14
Appears in Collections:National Heart and Lung Institute