title: Persistence of asthma following allergen avoidance is associated with proTh2 myeloid dendritic cell activation.
abstract: BACKGROUND
  The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Pôle de Pneumologie, Université catholique de Louvain, Brussels, Belgium Walloon Institute for Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium Department of Chest Medicine, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Antoine
authors.initials: A
authors.lastname: Froidure
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Pôle de Pneumologie, Université catholique de Louvain, Brussels, Belgium Walloon Institute for Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium Department of Chest Medicine, Centre Hospitalier Universitaire de Mont-Godinne, Université catholique de Louvain, Yvoir, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Vandenplas
authors.affiliation: Department of Chest Medicine, Centre Hospitalier Universitaire de Mont-Godinne, Université catholique de Louvain, Yvoir, Belgium.
authors.forename: Vinciane
authors.initials: V
authors.lastname: D'Alpaos
authors.affiliation: Department of Chest Medicine, Centre Hospitalier Universitaire de Mont-Godinne, Université catholique de Louvain, Yvoir, Belgium.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Evrard
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Pôle de Pneumologie, Université catholique de Louvain, Brussels, Belgium Walloon Institute for Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium Department of Chest Medicine, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Charles
authors.initials: C
authors.lastname: Pilette
mesh_terms: D000485:Allergens; D059366:Asthma, Occupational / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D005433:Flour; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007840:Latex; D022423:Myeloid Cells / Q000502:physiology*; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000502:physiology
chemical_list: D000485:Allergens; D018793:Interleukin-13; D015848:Interleukin-5; D007840:Latex; D061027:Programmed Cell Death 1 Ligand 2 Protein
keywords: Allergic lung disease; Asthma; Asthma Mechanisms; Occupational Lung Disease