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Title:
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Efferocytosis promotes suppressive effects on dendritic cells through prostaglandin E2 production in the context of autoimmunity
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Author:
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Pujol-Autonell, Irma; Ampudia, Rosa Maria; Planas, Raquel; Marin-Gallen, Silvia; Carrascal, Jorge; Sanchez, Alex; Marin, Ana; Puig-Domingo, Manuel; Pujol-Borrell, Ricardo; Verdaguer Autonell, Joan; Vives Pi, Marta
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Notes:
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Introduction: Efferocytosis is a crucial process by which apoptotic cells are cleared by phagocytes, maintaining immune
tolerance to self in the absence of inflammation. Peripheral tolerance, lost in autoimmune processes, may be restored by the
administration of autologous dendritic cells loaded with islet apoptotic cells in experimental type 1 diabetes.
Objective: To evaluate tolerogenic properties in dendritic cells induced by the clearance of apoptotic islet cells, thus
explaining the re-establishment of tolerance in a context of autoimmunity.
Methods: Bone marrow derived dendritic cells from non-obese diabetic mice, a model of autoimmune diabetes, were
generated and pulsed with islet apoptotic cells. The ability of these cells to induce autologous T cell proliferation and to
suppress mature dendritic cell function was assessed, together with cytokine production. Microarray experiments were
performed using dendritic cells to identify differentially expressed genes after efferocytosis.
Results: Molecular and functional changes in dendritic cells after the capture of apoptotic cells were observed. 1) Impaired
ability of dendritic cells to stimulate autologous T cell proliferation after the capture of apoptotic cells even after
proinflammatory stimuli, with a cytokine profile typical for immature dendritic cells. 2) Suppressive ability of mature
dendritic cell function. 3) Microarray-based gene expression profiling of dendritic cells showed differential expression of
genes involved in antigen processing and presentation after efferocytosis. 4) Prostaglandin E2 increased production was
responsible for immunosuppressive mechanism of dendritic cells after the capture of apoptotic cells.
Conclusions: The tolerogenic behaviour of dendritic cells after islet cells efferocytosis points to a mechanism of silencing
potential autoreactive T cells in the microenvironment of autoimmunity. Our results suggest that dendritic cells may be
programmed to induce specific immune tolerance using apoptotic cells; this is a viable strategy for a variety of autoimmune
diseases.
This work was supported by grants from the Fondo de Investigaciones Sanitarias (PS09/00253 and PI12/00195) of the Carlos III Institute of Health, www.isciii.es. RP was supported by the Instituto de Salud Carlos III of the Spanish National Institute of Health (FIS05/00418). MVP is funded by the stabilization program of Miguel Servet biomedical researchers and RMA by the program of research technicians of the Instituto de Salud Carlos III and Direcció d’Estrategia i Coordinacio, Health Dept. of the Catalonian Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
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Rights:
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cc-by, (c) Pujol-Autonell et al., 2013
http://creativecommons.org/licenses/by/3.0/es/
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Document type:
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article
publishedVersion |
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Published by:
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Public Library of Science
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