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Persistence of asthma following allergen avoidance is associated with proTh2 myeloid dendritic cell activation
  1. Antoine Froidure1,2,3,
  2. Olivier Vandenplas1,2,4,
  3. Vinciane D'Alpaos4,
  4. Geneviève Evrard4,
  5. Charles Pilette1,2,3
  1. 1Institut de Recherche Expérimentale et Clinique, Pôle de Pneumologie, Université catholique de Louvain, Brussels, Belgium
  2. 2Walloon Institute for Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium
  3. 3Department of Chest Medicine, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
  4. 4Department of Chest Medicine, Centre Hospitalier Universitaire de Mont-Godinne, Université catholique de Louvain, Yvoir, Belgium
  1. Correspondence to Professor Charles Pilette, Institut de Recherche Expérimentale et Clinique, Pôle de Pneumologie, Université catholique de Louvain and Walloon Institute for Excellence in Lifesciences and Biotechnology (WELBIO), Avenue Hippocrate, 54/B1.04-04, Brussels B-1200, Belgium; charles.pilette{at}uclouvain.be

Abstract

Background The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown.

Objectives We explored whether type 1 myeloid dendritic cell (mDC) dysfunction could be involved in the persistence of asthma, studying the controlled setting of occupational asthma after allergen avoidance.

Methods We recruited 32 patients with occupational asthma to flour or latex ascertained by specific inhalation challenge and who were no longer exposed to the causal allergen. Leukapheresis was performed in each patient to isolate and characterise blood type 1 mDCs, and their functionality was studied in coculture with allogeneic CD4+ T cells from controls.

Results At follow-up, 11/32 patients (34%) were characterised by the absence of symptoms and non-specific bronchial hyper-responsiveness to histamine and were considered to be cured. When compared with cured patients, mDCs from patients with persistent disease increased the production of interleukin (IL) 5 and IL-13 by CD4+ T cells, and upregulated programmed death ligand 2 (PD-L2) upon allergen pulsing. In addition, IL-5 and IL-13 responses could be reversed by exogenous IL-12, as well as by PD-L2 blockade.

Conclusions This study indicates that pro-Th2 features of mDCs correlate with disease activity in asthma after cessation of exposure to the causal allergen. The findings also highlight that the Th2 programming by dendritic cells is flexible and partly mediated by PD-L2.

  • Allergic lung disease
  • Asthma
  • Asthma Mechanisms
  • Occupational Lung Disease

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