title: Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in patients with allergic rhinitis and asthma.
abstract: BACKGROUND
  Myeloid dendritic cells (mDCs) and costimulatory molecules such as ICOSL/B7H2 play a pivotal role in murine experimental asthma, while little is known in human allergic disease. The aim of this study was to characterize the phenotype and ICOSL expression of mDCs from allergic rhinitis patients (AR) and their functional correlates on mDC regulation of T cell responses.
  
  
  METHODS
  Human blood myeloid, CD1c(+) DCs were isolated from AR or healthy controls. Expression of costimulatory molecules inducible costimulatory ligand (ICOSL) and programmed death ligand 1 (PD-L1) was analysed in blood mDCs by flow cytometry and in nasal tissue biopsies by dual immunostaining. Blood mDCs were cocultured with (allogeneic) CD4(+) T cells before immunoassays for cytokine responses.
  
  
  RESULTS
  mDCs from AR patients expressed a lower level of ICOSL, in both blood and nasal tissue. mDCs from AR were constitutively primed to induce Th2 cytokines and TNF in allogeneic CD4(+) T cells, while no difference was observed for IFN-γ or IL-10. Production of IL-10 and IL-12 did not differ between AR and control mDCs. Blockade of ICOSL in control DCs up-regulated IL-13 but not IFN-γ in cocultures with T cells, while PD-L1 blockade up-regulated both IL-13 and IFN-γ.
  
  
  CONCLUSIONS
  Our data show that mDCs from patients with AR display impaired expression of ICOSL, and this defect licenses mDCs to promote aberrant IL-13- and IL-5-producing Th2 cell responses.
authors.affiliation: Pôle Pneumologie, ORL & Dermatologie, Institut de Recherche Expérimentale & Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium; Institute for Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Cliniques Universitaires St-Luc, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Shen
authors.forename: C
authors.initials: C
authors.lastname: Hupin
authors.forename: A
authors.initials: A
authors.lastname: Froidure
authors.forename: B
authors.initials: B
authors.lastname: Detry
authors.forename: C
authors.initials: C
authors.lastname: Pilette
mesh_terms: D000328:Adult; D000368:Aged; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D065631:Rhinitis, Allergic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D039741:Antigens, Dermatophagoides; D060890:B7-H1 Antigen; D016207:Cytokines; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D007073:Immunoglobulin E; D000094632:Thymic Stromal Lymphopoietin
keywords: ICOSL (B7H2); PD-L1; TSLP; Th1/Th2 cells; allergy; costimulation; human dendritic cells; myeloid DC; nasal mucosa; tolerance