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IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke

Chen, K and Pociask, DA and McAleer, JP and Chan, YR and Alcorn, JF and Kreindler, JL and Keyser, MR and Shapiro, SD and Houghton, AMG and Kolls, JK and Zheng, M (2011) IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke. PLoS ONE, 6 (5).

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Chronic Obstructive Pulmonary Disease (COPD) is characterized by airspace enlargement and peribronchial lymphoid follicles; however, the immunological mechanisms leading to these pathologic changes remain undefined. Here we show that cigarette smoke is a selective adjuvant that augments in vitro and in vivo Th17, but not Th1, cell differentiation via the aryl hydrocarbon receptor. Smoke exposed IL-17RA-/- mice failed to induce CCL2 and MMP12 compared to WT mice. Remarkably, in contrast to WT mice, IL-17RA-/- mice failed to develop emphysema after 6 months of cigarette smoke exposure. Taken together, these data demonstrate that cigarette smoke is a potent Th17 adjuvant and that IL-17RA signaling is required for chemokine expression necessary for MMP12 induction and tissue emphysema. © 2011 Chen et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Chen, K
Pociask, DA
McAleer, JP
Chan, YR
Alcorn, JFjfa9@pitt.eduJFA9
Kreindler, JL
Keyser, MR
Shapiro, SDsds33@pitt.eduSDS33
Houghton, AMG
Kolls, JK
Zheng, M
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 June 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0020333
Refereed: Yes
MeSH Headings: Adjuvants, Immunologic--pharmacology; Animals; Bronchi--cytology; Bronchoalveolar Lavage; Cell Differentiation--immunology; Chemokine CCL2--genetics; Chemokine CCL2--metabolism; Emphysema--etiology; Emphysema--immunology; Emphysema--metabolism; Female; Gene Expression Regulation--immunology; Humans; Macrophages--immunology; Macrophages--metabolism; Matrix Metalloproteinase 12--genetics; Matrix Metalloproteinase 3--genetics; Mice; Mucous Membrane--immunology; Mucous Membrane--metabolism; Receptors, Aryl Hydrocarbon--metabolism; Receptors, Interleukin-17--metabolism; Sequence Analysis, RNA; Smoke--adverse effects; Th17 Cells--cytology; Th17 Cells--immunology; Tobacco--immunology; Transcriptional Activation--immunology
Other ID: NLM PMC3103542
PubMed Central ID: PMC3103542
PubMed ID: 21647421
Date Deposited: 30 Aug 2012 15:01
Last Modified: 22 Jun 2021 14:55


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