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Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in patients with allergic rhinitis and asthma

Onglets principaux

Shen, Chong [UCL] Hupin, Cloé [UCL] Froidure, Antoine [UCL] Detry, Bruno [UCL] Pilette, Charles [UCL]

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.

Type de document Article de périodique (Journal article) – Article de recherche
Type d'accès Accès restreint
Année de publication 2014
Langue Anglais
Information sur le périodique "Clinical and Experimental Allergy" - Vol. 44, no. 6, p. 831-41 (Jun 2014)
Peer reviewed oui
Editeur Blackwell Scientific Publications ((United Kingdom) Oxford)
issn 0954-7894
e-issn 1365-2222
Statut de la publication Publié
Affiliations UCL - SSS/IREC/PNEU-Pôle de Pneumologie, ORL et Dermatologie
UCL - (SLuc) Service de pneumologie
UCL - (SLuc) Service de médecine interne et maladies infectieuses (MIMI)
UCL - (SLuc) Service d'oto-rhino-laryngologie
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Référence bibliographique Shen, Chong ; Hupin, Cloé ; Froidure, Antoine ; Detry, Bruno ; Pilette, Charles. Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in patients with allergic rhinitis and asthma. In: Clinical and Experimental Allergy, Vol. 44, no. 6, p. 831-41 (Jun 2014)
Permalien http://hdl.handle.net/2078.1/145096