ORIGINAL ARTICLE Persistence of asthma following allergen avoidance is associated with proTh2 myeloid dendritic cell activation Antoine Froidure, 1,2,3 Olivier Vandenplas, 1,2,4 Vinciane D’Alpaos, 4 Geneviève Evrard, 4 Charles Pilette 1,2,3 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ thoraxjnl-2014-206364). 1 Institut de Recherche Expérimentale et Clinique, Pôle de Pneumologie, Université catholique de Louvain, Brussels, Belgium 2 Walloon Institute for Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium 3 Department of Chest Medicine, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium 4 Department of Chest Medicine, Centre Hospitalier Universitaire de Mont-Godinne, Université catholique de Louvain, Yvoir, Belgium 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@uclouvain.be OV and CP contributed equally. Received 24 September 2014 Revised 19 May 2015 Accepted 5 June 2015 Published Online First 23 June 2015 To cite: Froidure A, Vandenplas O, D’Alpaos V, et al. Thorax 2015;70: 967–973. 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. INTRODUCTION The mechanisms associated with asthma recovery or persistence have almost never been explored. In addition, although allergen avoidance is recom- mended in the management of allergic asthma, strategies to reduce allergen exposure failed to show a clear benefit. 1 In this regard, IgE-mediated occupational asthma (OA) induced by high molecu- lar weight agents is a specific condition that offers the possibility to strictly control exposure to the causal allergen. Nonetheless, the outcome of OA following cessation of exposure is disappointing, with only about a third of the patients recovering from their symptoms and non-specific bronchial hyper-responsiveness (NSBHR). 23 Studies on OA have shown that failure to improve NSBHR upon allergen avoidance was associated with higher levels of inflammatory cytokines in sputum and persistent airway inflammation, 45 but the immune mechan- isms involved remain unknown. Type 1 myeloid dendritic cells (mDCs) are pro- fessional antigen-presenting cells that play a key role in the initiation of immune responses. Their role in asthma inception has been highlighted for 15 years. 6 Besides their ability to present allergens to naïve T cells, mDCs are able to shape the immune response through the secretion of cyto- kines and expression of costimulatory molecules. The role of some costimulatory molecules has been recently explored in human asthma, 7 including the first and second ligands to programmed death-1 (PD-L1 and PD-L2) 89 and the ligand to immune costimulator, 10 as factors involved in the intrinsic pro-Th2 bias of mDCs from patients with asthma. 11 12 mDCs from patients with allergic asthma also have an intrinsic propensity to respond to proallergic epithelial cytokines such as thymic stromal lymphopoietin. 13 Given the pivotal role of mDCs in asthma incep- tion and progression, we hypothesised that these cells might be involved in asthma recovery or persistence following allergen avoidance. In this study, the phenotype and function of mDCs were correlated to the clinical outcome of asthma (ie, persistence vs remission) in the well controlled setting of allergen- driven OA following cessation of exposure to the causal allergen. Key messages What is the key question? ▸ The natural history of asthma includes in some patients periods of disease remission, but the underlying mechanisms are unknown. What is the bottom line? ▸ We studied myeloid dendritic cell (mDC) functionality in a well controlled setting, namely patients with occupational asthma with either remission or persistence following complete allergen avoidance. Why read on? ▸ This study shows that blood mDCs from patients with occupational asthma and persistent disease despite allergen avoidance are imprinted with pro-Th2 activity. Froidure A, et al. Thorax 2015;70:967–973. doi:10.1136/thoraxjnl-2014-206364 967 Respiratory research on June 4, 2020 by guest. 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