Human bronchial epithelium orchestrates dendritic cell activation in severe asthma

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

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asthma / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / immunology
  • Dendritic Cells / immunology*
  • Epithelial Cells / immunology*
  • Female
  • Humans
  • Interleukin-33 / immunology
  • Interleukin-8 / immunology
  • Male
  • Middle Aged
  • Th2 Cells / immunology

Substances

  • CXCL8 protein, human
  • Cytokines
  • IL33 protein, human
  • Interleukin-33
  • Interleukin-8
  • thymic stromal lymphopoietin

Associated data

  • ClinicalTrials.gov/NCT00793676