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

Research output: Contribution to journalArticleResearchpeer-review

63 Citations (Scopus)

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