Human bronchial epithelium orchestrates dendritic cell activation in severe asthma

[摘要] 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 epithelialxe2x80x93dendritic crosstalk in normal and diseased conditions; and because ultrafine particulate matter may affect asthmatic airways; we investigated its impact on this crosstalk. Airxe2x80x93liquid 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 epithelialxe2x80x93dendritic responses. We conclude that control moDC cannot rescue the hyperresponsive airway epithelium of severe asthmatics.

[学科分类] 呼吸医学