title: Polycyclic aromatic hydrocarbons reciprocally regulate IL-22 and IL-17 cytokines in peripheral blood mononuclear cells from both healthy and asthmatic subjects.
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.
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Coline
authors: C
authors: Plé
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Ying
authors: Y
authors: Fan
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Saliha
authors: S
authors: Ait Yahia
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Han
authors: H
authors: Vorng
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Laetitia
authors: L
authors: Everaere
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Cécile
authors: C
authors: Chenivesse
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Joanne
authors: J
authors: Balsamelli
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Imane
authors: I
authors: Azzaoui
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France.
authors: Patricia
authors: P
authors: de Nadai
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France; Clinique des Maladies Respiratoires et Centre Hospitalier Régional et Universitaire de Lille, F-59037, Lille, France.
authors: Benoit
authors: B
authors: Wallaert
authors: CNRS SysDiag-UMR3145 Cap delta, 1682 rue de la Valsière, F-34184, Montpellier Cedex 4, France.
authors: Gwendal
authors: G
authors: Lazennec
authors: Institut National de la Santé et de la Recherche Médicale, U1019, F-59019, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, F-59019, Lille, France; CNRS UMR 8204, F-59000, Lille, France; Univ Lille Nord de France, F-59000, Lille, France; Clinique des Maladies Respiratoires et Centre Hospitalier Régional et Universitaire de Lille, F-59037, Lille, France.
authors: Anne
authors: A
authors: Tsicopoulos
mesh_terms: D000328:Adult; D001249:Asthma / Q000209:etiology* / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000633:toxicity; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation; D001335:Vehicle Emissions / Q000032:analysis; D000097043:Interleukin-22
chemical_list: D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; D020381:Interleukin-17; D007378:Interleukins; D048031:JNK Mitogen-Activated Protein Kinases; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D019869:Phosphatidylinositol 3-Kinases; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D001335:Vehicle Emissions; D000097043:Interleukin-22; C508717:IL17A protein, human; C539738:RORA protein, human; C539900:RORC protein, human; C569463:CYP1A1 protein, human