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

• Published in: PloS one Vol. 10; no. 4; p. e0122372
• Main Authors: Plé, Coline, Fan, Ying, Ait Yahia, Saliha, Vorng, Han, Everaere, Laetitia, Chenivesse, Cécile, Balsamelli, Joanne, Azzaoui, Imane, de Nadai, Patricia, Wallaert, Benoit, Lazennec, Gwendal, Tsicopoulos, Anne
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.04.2015; Public Library of Science (PLoS)
• Subjects: Adult; Allergies; Allergology; Antigens; Aromatic compounds; Asthma; Asthma - etiology; Asthma - metabolism; Benzo(a)pyrene - toxicity; Blood; Blood cells; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - metabolism; Cells, Cultured; Cytochrome P-450 CYP1A1 - metabolism; Cytokines; Diesel engines; Down-Regulation; Female; Gene expression; Health aspects; Humans; Immunology; Infections; Inflammation; Interleukin-17 - genetics; Interleukin-17 - metabolism; Interleukin-22; Interleukins; Interleukins - genetics; Interleukins - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Life Sciences; Ligands; Lymphocytes; Male; Middle Aged; Muscles; Nuclear Receptor Subfamily 1, Group F, Member 1 - metabolism; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; 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; Th17 Cells - cytology; Th17 Cells - metabolism; Transcription factors; Up-Regulation; Vehicle Emissions - analysis; France; Flow cytometry; Transcription factors; Cytokines; Secretion; Cloning; T cells; Kinase inhibitors; Asthma
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0122372

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.