Altered innate function of plasmacytoid dendritic cells restored by enzyme replacement therapy in Gaucher disease

Autor: Julie Graveleau, Stéphanie Giraudet, Antoine Néel, Mohamed Hamidou, Agathe Masseau, Caroline Terrien, Régis Josien, Bernard Grosbois, Cécile Braudeau, Marie Rimbert, Audrey Besançon
Přispěvatelé: Le Bihan, Sylvie, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire d’Immunologie [CHU Nantes] (Centre d’Immunomonitorage Nantes Atlantique - CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Faculté de Médecine - Université de Nantes, A grant from the Programme Hospitalier de Recherche Clinique Interregional 2009.
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Blood Cells, Molecules and Diseases
Blood Cells, Molecules and Diseases, 2013, 50 (4), pp.281-288. ⟨10.1016/j.bcmd.2013.01.001⟩
Blood Cells, Molecules and Diseases, Elsevier, 2013, 50 (4), pp.281-288. ⟨10.1016/j.bcmd.2013.01.001⟩
ISSN: 1079-9796
1096-0961
Popis: Background Gaucher disease (GD) is caused by an autosomal-recessive deficiency of β-glucocerebrosidase leading to an accumulation of glucosylceramide in monocytes/macrophage lineage. We analyzed immune cells and especially the function of dendritic cells to evaluate the potential impact of glucosylceramide accumulation in these cells and its possible role in infections and malignancies usually described in this pathology. These analyses were performed for each patient without and under enzyme replacement therapy. Methods Seven GD patients were studied and compared with healthy volunteers. Immune cells (B cells, T cells, NK, dendritic cells), were analyzed by flow cytometry directly on whole blood. Cytokine production by blood dendritic cells was assessed after stimulation by toll-like receptor ligands. Cytokines in sera were measured using a multiplex assay. Results GD patients displayed decreased numbers of NK cells, γδ2 T cells and increased frequency of memory CD4 + CD45RO + T cells, when compared to healthy controls. Numbers of dendritic cells (myeloid (mDC) and plasmacytoid (pDC) dendritic cells) were also decreased. We demonstrated that pDC from GD patients exhibited a decrease in IFNα production after TLR9 stimulation compared to controls. Importantly, enzyme replacement therapy restored pDC function. Finally, we observed an increase of IL-8 and IL-18 in GD patient sera, which were reduced under enzyme replacement therapy. Conclusions Our data confirm that patients with GD exhibit altered numbers of innate and T lymphocytes and show for the first time that pDC from GD patients exhibit altered responsiveness to TLR9. These alterations could contribute to a decreased response to pathogens and could favor the development of malignancies.
Databáze: OpenAIRE
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