Journal Article

Polycyclic Aromatic Hydrocarbons Reciprocally Regulate IL-22 and IL-17 Cytokines in Peripheral Blood Mononuclear Cells from Both Healthy and Asthmatic Subjects

Everaere, Laetitia, Balsamelli, Joanne, de Nadai, Patricia, Vorng, Han, Tsicopoulos, Anne, Chenivesse, Cécile, Fan, Ying, Ait Yahia, Saliha, Lazennec, Gwendal, Plé, Coline, Azzaoui, Imane, Wallaert, Benoit

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 1-Phosphatidylinositol 3-kinase / Adult / Allergies / Allergology / Antigens / Aromatic compounds / Asthma / Asthma - etiology / Asthma - metabolism / Benzo(a)pyrene / Benzo(a)pyrene - toxicity / Blood / Blood cells / CD4 antigen / CD4-Positive T-Lymphocytes - cytology / CD4-Positive T-Lymphocytes - metabolism / Cells, Cultured / Cytochrome P-450 CYP1A1 - metabolism / Cytochrome P450 / Cytokines / Diesel engines / Down-Regulation / Female / Gene expression / Health aspects / Helper cells / Humans / Immunology / Infections / Inflammation / Interleukin 17 / Interleukin 22 / Interleukin-17 - genetics / Interleukin-17 - metabolism / Interleukins / Interleukins - genetics / Interleukins - metabolism / JNK Mitogen-Activated Protein Kinases - metabolism / JNK protein / Leukocytes (mononuclear) / Leukocytes (neutrophilic) / Leukocytes, Mononuclear - cytology / Leukocytes, Mononuclear - metabolism / Life Sciences / Ligands / Lymphocytes / Lymphocytes T / Male / Middle Aged / Muscles / Nuclear Receptor Subfamily 1, Group F, Member 1 - metabolism / Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism / Peripheral blood mononuclear cells / Phosphatidylinositol 3-Kinases - metabolism / Physiological aspects / Polycyclic aromatic hydrocarbons / Polycyclic Aromatic Hydrocarbons - toxicity / Pyrene / Receptors, Aryl Hydrocarbon - chemistry / Receptors, Aryl Hydrocarbon - metabolism / Risk factors / RNA, Messenger - metabolism / Smooth muscle / Th17 Cells - cytology / Th17 Cells - metabolism / Transcription factors / Up-Regulation / Vehicle Emissions - analysis