title: Myeloid dendritic cells are primed in allergic asthma for thymic stromal lymphopoietin-mediated induction of Th2 and Th9 responses.
abstract: BACKGROUND
  Type 1 myeloid dendritic cells (mDCs) contribute to inception of allergic asthma (AA) and are regulated by epithelial-derived cytokines.
  
  
  OBJECTIVE
  To evaluate whether mDCs from AA patients are primed for thymic stromal lymphopoietin (TSLP)-driven responses.
  
  
  METHODS
  mDCs from 18 AA patients and 15 controls were purified using immunomagnetic sorting. Cells were pulsed with TSLP or Dermatophagoides pteronyssinus (Der p) allergen, before FACS phenotyping and co-culture with allogeneic CD4+ T cells. Bronchial biopsies from 15 AA patients and four controls were immunostained for CD1c and TSLP receptor (TSLPR).
  
  
  RESULTS
  Allergic asthma patients had a higher proportion of TSLPR+ mDCs, in blood and bronchial mucosa. When compared to mDCs from controls, both TSLP- and Der p-pulsed blood mDCs from AA patients induced increased polarization of CD4+ T cells into Th2 cells (IL-5, IL-13, and GATA3+), while only TSLP-mDCs promoted Th9 cells (IL-9 and PU.1+ /IRF4+). In addition, OX40L was induced upon TSLP stimulation and was required for the induction of Th2, but not Th9, cells. In contrast, development of Th9 cells in this model depended on TGF-β1.
  
  
  CONCLUSIONS
  Our data indicate overlapping but partially distinct effects of TSLP and Der p allergen pathways, showing that DCs are primed in human asthma for TSLP-driven induction of both Th2 and Th9 cells. This novel TSLP/mDC/Th9 axis operates through a distinct, OX40L-independent pathway. These data further highlight the TSLP pathway as a relevant target in human asthma.
authors.affiliation: Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Walloon Institute for Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium; Cliniques Universitaires Saint-Luc, service de Pneumologie, Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Froidure
authors.forename: C
authors.initials: C
authors.lastname: Shen
authors.forename: D
authors.initials: D
authors.lastname: Gras
authors.forename: J
authors.initials: J
authors.lastname: Van Snick
authors.forename: P
authors.initials: P
authors.lastname: Chanez
authors.forename: C
authors.initials: C
authors.lastname: Pilette
mesh_terms: D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins / Q000276:immunology; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016022:Case-Control Studies; D003546:Cysteine Endopeptidases / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D053278:OX40 Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C498762:CRLF2 protein, human; D016207:Cytokines; D053278:OX40 Ligand; D018121:Receptors, Cytokine; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1; D000094632:Thymic Stromal Lymphopoietin
keywords: Th9; asthma; interleukin-9; myeloid dendritic cells; thymic stromal lymphopoietin