bronchial epithelium orchestrates dendritic cell activation in severe
Laure de Senneville1
and Pascal Chanez1,3,5
INSERM 1067/CNRS 7333, Marseille, France,?2Departement
des Maladies respiratoires, CHU Montpellier and PhyMedExp,
Universit? de Montpellier, INSERM U1046, CNRS UMR 9214,
H?pital Arnaud de Villeneuve, Montpellier, France,?3Aix-Marseille
Universit?, Marseille, France,?4APHM
(Assistance Publique H?pitaux de Marseille), Laboratoire
d'Immunologie, H?pital de la Conception, Marseille,
France,?5APHM, Clinique des bronches,
de l'allergie et du Sommeil, H?pital Nord, Marseille, France
The innate immune response is
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
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,
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.