TY - JOUR T1 - Human bronchial epithelium orchestrates dendritic cell activation in severe asthma JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02399-2016 VL - 49 IS - 3 SP - 1602399 AU - Delphine Gras AU - Asuncion Martinez-Anton AU - Arnaud Bourdin AU - Celine Garulli AU - Laure de Senneville AU - Isabelle Vachier AU - Joana Vitte AU - Pascal Chanez Y1 - 2017/03/01 UR - http://erj.ersjournals.com/content/49/3/1602399.abstract N2 - 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 established in 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.Normal or asthmatic status of bronchial epithelium shapes the function of the epithelial–dendritic cell trophic unit http://ow.ly/teQ43085KRf ER -