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
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Support statement: This work was supported by Société Française d'Allergologie, Fond de Recherche en Santé Respiratoire, ARARD and ANR. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com
- Received May 23, 2016.
- Accepted January 3, 2017.
- Copyright ©ERS 2017