Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette smoke-induced lung inflammation in mice

Bozinovski, S, Seow, H, Chan, S, Anthony, D, McQualter, J, Hansen, M, Jenkins, B, Anderson, G and Vlahos, R 2015, 'Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette smoke-induced lung inflammation in mice', Clinical Science, vol. 129, no. 9, pp. 785-796.


Document type: Journal Article
Collection: Journal Articles

Attached Files
Name Description MIMEType Size
n2006053991.pdf Published Version application/pdf 900.57KB
Title Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette smoke-induced lung inflammation in mice
Author(s) Bozinovski, S
Seow, H
Chan, S
Anthony, D
McQualter, J
Hansen, M
Jenkins, B
Anderson, G
Vlahos, R
Year 2015
Journal name Clinical Science
Volume number 129
Issue number 9
Start page 785
End page 796
Total pages 12
Publisher Portland Press Limited
Abstract Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). Interleukin-17A (IL-17A) is a pivotal cytokine that regulates lung immunity and inflammation. The aim of this study was to investigate how IL-17A regulates CS-induced lung inflammation in vivo . IL-17A KO mice and neutralisation of IL-17A in WT mice reduced macrophage and neutrophil recruitment and CCL2, CCL3 and MMP-12 mRNA expression in response to acute CS exposure. IL-17A expression was increased in NOD SCID mice with non-functional B and T cells over a 4 week CS exposure period, where macrophages accumulated to the same extent as WT mice. Gene expression analysis by QPCR of isolated immune cell subsets detected increased levels of IL-17A transcript in macrophages, neutrophils and NK/NKT cells in the lungs of CS-exposed mice. In order to further explore the relative contribution of innate immune cellular sources, intracellular IL-17A staining was performed. Here, we demonstrate that CS exposure primes NK, NKT and γδ T cells to produce more IL-17A protein and CS alone increased the frequency of IL17+ γδ T cells in the lung, whereas IL-17A protein was not detected in macrophages and neutrophils. Our data suggest that activation of innate cellular sources of IL-17A is an essential mediator of macrophage accumulation in CS-exposed lungs. Targeting non-conventional T cell sources of IL-17A may offer an alternative strategy to reduce pathogenic macrophages in COPD.
Subject Respiratory Diseases
Clinical Sciences not elsewhere classified
DOI - identifier 10.1042/CS20140703
Copyright notice Copyright 2015 The Author(s)
ISSN 1470-8736
Additional Notes Creative Commons Licence
This work is licensed under a Creative Commons Attribution 3.0 Australia License.
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Altmetric details:
Access Statistics: 32 Abstract Views, 22 File Downloads  -  Detailed Statistics
Created: Wed, 28 Oct 2015, 10:15:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us