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

Steven Bozinovski, Huei Jiunn Seow, Sheau Pyng Jamie Chan, Desiree A Anthony, Jonathan Luke McQualter, Michelle J Hansen, Brendan John Jenkins, Gary Anderson, Ross Vlahos

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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 gammadelta T cells to produce more IL-17A protein and CS alone increased the frequency of IL17+ gammadelta 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.
Original languageEnglish
Pages (from-to)785 - 796
Number of pages12
JournalClinical Science
Volume129
Issue number9
DOIs
Publication statusPublished - 2015

Cite this

Bozinovski, S., Seow, H. J., Chan, S. P. J., Anthony, D. A., McQualter, J. L., Hansen, M. J., ... Vlahos, R. (2015). Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette- smoke-induced lung inflammation in mice. Clinical Science, 129(9), 785 - 796. https://doi.org/10.1042/CS20140703
Bozinovski, Steven ; Seow, Huei Jiunn ; Chan, Sheau Pyng Jamie ; Anthony, Desiree A ; McQualter, Jonathan Luke ; Hansen, Michelle J ; Jenkins, Brendan John ; Anderson, Gary ; Vlahos, Ross. / Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette- smoke-induced lung inflammation in mice. In: Clinical Science. 2015 ; Vol. 129, No. 9. pp. 785 - 796.
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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 gammadelta T cells to produce more IL-17A protein and CS alone increased the frequency of IL17+ gammadelta 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.",
author = "Steven Bozinovski and Seow, {Huei Jiunn} and Chan, {Sheau Pyng Jamie} and Anthony, {Desiree A} and McQualter, {Jonathan Luke} and Hansen, {Michelle J} and Jenkins, {Brendan John} and Gary Anderson and Ross Vlahos",
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Bozinovski, S, Seow, HJ, Chan, SPJ, Anthony, DA, McQualter, JL, Hansen, MJ, Jenkins, BJ, Anderson, G & 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. https://doi.org/10.1042/CS20140703

Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette- smoke-induced lung inflammation in mice. / Bozinovski, Steven; Seow, Huei Jiunn; Chan, Sheau Pyng Jamie; Anthony, Desiree A; McQualter, Jonathan Luke; Hansen, Michelle J; Jenkins, Brendan John; Anderson, Gary; Vlahos, Ross.

In: Clinical Science, Vol. 129, No. 9, 2015, p. 785 - 796.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Bozinovski, Steven

AU - Seow, Huei Jiunn

AU - Chan, Sheau Pyng Jamie

AU - Anthony, Desiree A

AU - McQualter, Jonathan Luke

AU - Hansen, Michelle J

AU - Jenkins, Brendan John

AU - Anderson, Gary

AU - Vlahos, Ross

PY - 2015

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N2 - 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 gammadelta T cells to produce more IL-17A protein and CS alone increased the frequency of IL17+ gammadelta 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.

AB - 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 gammadelta T cells to produce more IL-17A protein and CS alone increased the frequency of IL17+ gammadelta 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.

UR - http://www.clinsci.org/content/ppclinsci/129/9/785.full.pdf

U2 - 10.1042/CS20140703

DO - 10.1042/CS20140703

M3 - Article

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EP - 796

JO - Clinical Science and Molecular Medicine

JF - Clinical Science and Molecular Medicine

SN - 0009-9287

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