Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Animals
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Bronchi / cytology
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Bronchoalveolar Lavage
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Cell Differentiation / immunology
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism*
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Emphysema / etiology
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Emphysema / immunology*
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Emphysema / metabolism
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Female
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Gene Expression Regulation / immunology*
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Humans
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Macrophages / immunology*
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Macrophages / metabolism
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Matrix Metalloproteinase 12 / genetics
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Matrix Metalloproteinase 3 / genetics
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Mice
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Mucous Membrane / immunology
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Mucous Membrane / metabolism
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Nicotiana / immunology*
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Receptors, Aryl Hydrocarbon / metabolism
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Receptors, Interleukin-17 / metabolism*
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Sequence Analysis, RNA
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Smoke / adverse effects*
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Th17 Cells / cytology
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Th17 Cells / immunology
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Transcriptional Activation / immunology
Substances
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Adjuvants, Immunologic
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Chemokine CCL2
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IL17RA protein, human
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Receptors, Aryl Hydrocarbon
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Receptors, Interleukin-17
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Smoke
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 12