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Eur Respir J. 2017 Mar 8;49(3). pii: 1602399. doi: 10.1183/13993003.02399-2016. Print 2017 Mar.

Human bronchial epithelium orchestrates dendritic cell activation in severe asthma.

Author information

1
UMR INSERM 1067/CNRS 7333, Marseille, France delphine.gras@univ-amu.fr.
2
UMR INSERM 1067/CNRS 7333, Marseille, France.
3
Departement des Maladies respiratoires, CHU Montpellier and PhyMedExp, Université de Montpellier, INSERM U1046, CNRS UMR 9214, Hôpital Arnaud de Villeneuve, Montpellier, France.
4
Aix-Marseille Université, Marseille, France.
5
APHM (Assistance Publique Hôpitaux de Marseille), Laboratoire d'Immunologie, Hôpital de la Conception, Marseille, France.
6
APHM, Clinique des bronches, de l'allergie et du Sommeil, Hôpital Nord, Marseille, France.

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 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00793676.

PMID:
28275176
DOI:
10.1183/13993003.02399-2016
[Indexed for MEDLINE]
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