Campbell, Eric L. and Bruyninckx, Walter J. and Kelly, Caleb J. and Glover, Louise and McNamee, Eóin N. and Bowers, Brittelle E. and Bayless, Amanda J. and Scully, Melanie and Saeedi, Bejan J. and Golden-Mason, Lucy and Ehrentraut, Stefan F. and Curtis, Valerie F. and Burgess, Adrianne and Garvey, John F. and Sorensen, Amber and Nemenoff, Raphael and Jedlicka, Paul and Taylor, Cormac T and Kominsky, Douglas J and Colgan, S.P. (2014) Transmigrating Neutrophils Shape the Mucosal Microenvironment through Localized Oxygen Depletion to Influence Resolution of Inflammation. Immunity, 40 (1). pp. 66-77. ISSN 1097-4180

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Abstract

Acute intestinal inflammation involves early accumulation of neutrophils (PMNs) followed by either resolution or progression to chronic inflammation. Based on recent evidence that mucosal metabolism influences disease outcomes, we hypothesized that transmigrating PMNs influence the transcriptional profile of the surrounding mucosa. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by PMN-epithelial crosstalk. Transmigrating PMNs rapidly depleted microenvironmental O2 sufficiently to stabilize intestinal epithelial cell hypoxia-inducible factor (HIF). By utilizing HIF reporter mice in an acute colitis model, we investigated the relative contribution of PMNs and the respiratory burst to ‘‘inflammatory hypoxia’’ in vivo. CGD mice, lacking a respiratory burst, developed accentuated colitis compared to control, with exaggerated PMN infiltration and diminished inflammatory hypoxia. Finally, pharmacological HIF stabilization within the mucosa protected CGD mice from severe colitis. In conclusion, transcriptional imprinting by infiltrating neutrophils modulates the host response to inflammation, via localized O2 depletion, resulting in microenvironmental hypoxia and effective inflammatory resolution.

Item Type:	Article
Keywords:	Transmigrating; Neutrophils; Mucosal Microenvironment; Localized; Oxygen Depletion; Resolution; Inflammation;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12580
Identification Number:	https://doi.org/10.1016/j.immuni.2013.11.020
Depositing User:	Eoin McNamee
Date Deposited:	20 Mar 2020 11:15
Journal or Publication Title:	Immunity
Publisher:	Elsevier
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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