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

PLoS One. 2011;6(5):e20333. doi: 10.1371/journal.pone.0020333. Epub 2011 May 27.

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

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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

Substances

  • Adjuvants, Immunologic
  • Chemokine CCL2
  • IL17RA protein, human
  • Receptors, Aryl Hydrocarbon
  • Receptors, Interleukin-17
  • Smoke
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 12