Polycyclic aromatic hydrocarbons reciprocally regulate IL-22 and IL-17 cytokines in peripheral blood mononuclear cells from both healthy and asthmatic subjects

PLoS One. 2015 Apr 10;10(4):e0122372. doi: 10.1371/journal.pone.0122372. eCollection 2015.

Abstract

Pollution, including polycyclic aromatic hydrocarbons (PAH), may contribute to increased prevalence of asthma. PAH can bind to the Aryl hydrocarbon Receptor (AhR), a transcription factor involved in Th17/Th22 type polarization. These cells produce IL17A and IL-22, which allow neutrophil recruitment, airway smooth muscle proliferation and tissue repair and remodeling. Increased IL-17 and IL-22 productions have been associated with asthma. We hypothesized that PAH might affect, through their effects on AhR, IL-17 and IL-22 production in allergic asthmatics. Activated peripheral blood mononuclear cells (PBMCs) from 16 nonallergic nonasthmatic (NA) and 16 intermittent allergic asthmatic (AA) subjects were incubated with PAH, and IL-17 and IL-22 productions were assessed. At baseline, activated PBMCs from AA exhibited an increased IL-17/IL-22 profile compared with NA subjects. Diesel exhaust particle (DEP)-PAH and Benzo[a]Pyrene (B[a]P) stimulation further increased IL-22 but decreased IL-17A production in both groups. The PAH-induced IL-22 levels in asthmatic patients were significantly higher than in healthy subjects. Among PBMCs, PAH-induced IL-22 expression originated principally from single IL-22- but not from IL-17- expressing CD4 T cells. The Th17 transcription factors RORA and RORC were down regulated, whereas AhR target gene CYP1A1 was upregulated. IL-22 induction by DEP-PAH was mainly dependent upon AhR whereas IL-22 induction by B[a]P was dependent upon activation of PI3K and JNK. Altogether, these data suggest that DEP-PAH and B[a]P may contribute to increased IL22 production in both healthy and asthmatic subjects through mechanisms involving both AhR -dependent and -independent pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthma / etiology*
  • Asthma / metabolism
  • Benzo(a)pyrene / toxicity
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Cytochrome P-450 CYP1A1 / metabolism
  • Down-Regulation
  • Female
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-22
  • Interleukins / genetics
  • Interleukins / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / metabolism
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polycyclic Aromatic Hydrocarbons / toxicity*
  • RNA, Messenger / metabolism
  • Receptors, Aryl Hydrocarbon / chemistry
  • Receptors, Aryl Hydrocarbon / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / metabolism
  • Up-Regulation
  • Vehicle Emissions / analysis

Substances

  • IL17A protein, human
  • Interleukin-17
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Polycyclic Aromatic Hydrocarbons
  • RNA, Messenger
  • RORA protein, human
  • RORC protein, human
  • Receptors, Aryl Hydrocarbon
  • Vehicle Emissions
  • Benzo(a)pyrene
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1
  • Phosphatidylinositol 3-Kinases
  • JNK Mitogen-Activated Protein Kinases

Grants and funding

This study was supported by research grants from Agence Nationale de la Recherche (ANR CES), Région Nord Pas de Calais (IRENI), FEDER and Santelys. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.