title: Human bronchial epithelium orchestrates dendritic cell activation in severe asthma.
abstract: The innate immune response is impaired in asthma, with increased epithelial release of C-X-C motif chemokine ligand (CXCL)8, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). We hypothesised that dendritic cells might modulate the hyperresponsive epithelium in severe asthma.For this purpose, we investigated epithelial-dendritic crosstalk in normal and diseased conditions, and because ultrafine particulate matter may affect asthmatic airways, we investigated its impact on this crosstalk. Air-liquid interface cultures of human bronchial epithelial cells (HBEC) of control subjects (cHBEC) or severe asthma patients (saHBEC) were co-cultured with monocyte-derived dendritic cells (moDC).Increased release of CXCL8, TSLP and IL-33 from saHBEC contrasted with cHBEC producing CXCL10 and CCL2. Regarding moDC activation, saHBEC co-cultures induced only upregulation of CD86 expression, while cHBEC yielded full moDC maturation with HLA-DR, CD80, CD86 and CD40 upregulation. Particulate matter stimulation of HBEC had no effect on cHBEC but stimulated CXCL8 and IL-33 release in saHBEC. Particulate matter impaired epithelium signalling (TSLP, IL-33 and CXCL8) in saHBEC co-cultures despite C-C chemokine ligand 2 induction.Crosstalk between HBEC and moDC can be establishedin vitro, driving a T1-type response with cHBEC and a T2-type response with saHBEC. Normal or asthmatic status of HBEC differentially shapes the epithelial-dendritic responses. We conclude that control moDC cannot rescue the hyperresponsive airway epithelium of severe asthmatics.
authors.affiliation: UMR INSERM 1067/CNRS 7333, Marseille, France delphine.gras@univ-amu.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Gras
authors.affiliation: UMR INSERM 1067/CNRS 7333, Marseille, France.
authors.forename: Asuncion
authors.initials: A
authors.lastname: Martinez-Anton
authors.affiliation: Departement des Maladies respiratoires, CHU Montpellier and PhyMedExp, Université de Montpellier, INSERM U1046, CNRS UMR 9214, Hôpital Arnaud de Villeneuve, Montpellier, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bourdin
authors.affiliation: UMR INSERM 1067/CNRS 7333, Marseille, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Garulli
authors.affiliation: UMR INSERM 1067/CNRS 7333, Marseille, France.
authors.forename: Laure
authors.initials: L
authors.lastname: de Senneville
authors.affiliation: Departement des Maladies respiratoires, CHU Montpellier and PhyMedExp, Université de Montpellier, INSERM U1046, CNRS UMR 9214, Hôpital Arnaud de Villeneuve, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vachier
authors.affiliation: UMR INSERM 1067/CNRS 7333, Marseille, France.|Aix-Marseille Université, Marseille, France.|APHM (Assistance Publique Hôpitaux de Marseille), Laboratoire d'Immunologie, Hôpital de la Conception, Marseille, France.
authors.forename: Joana
authors.initials: J
authors.lastname: Vitte
authors.affiliation: UMR INSERM 1067/CNRS 7333, Marseille, France.|Aix-Marseille Université, Marseille, France.|APHM, Clinique des bronches, de l'allergie et du Sommeil, Hôpital Nord, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D000067596:Interleukin-33 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018418:Th2 Cells / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; C506536:IL33 protein, human; D000067596:Interleukin-33; D016209:Interleukin-8; D000094632:Thymic Stromal Lymphopoietin