Per citar aquest document: http://ddd.uab.cat/record/142366
Efferocytosis Promotes Suppressive Effects on Dendritic Cells through Prostaglandin E2 Production in the Context of Autoimmunity
Pujol Autonell, Irma (Hospital Germans Trias i Pujol)
Ampudia, Rosa-Maria (Hospital Germans Trias i Pujol)
Planas, Raquel (Hospital Germans Trias i Pujol)
Marin-Gallen, Silvia (Hospital Germans Trias i Pujol)
Carrascal, Jorge (Universitat de Lleida. Departament de Ciències Bàsiques)
Sanchez, Alex (Vall d'Hebron Hospitals. Institut de Recerca)
Marin, Ana (Hospital Germans Trias i Pujol)
Puig Domingo, Manuel (Institut de Recerca "Germans Trias i Pujol". Secció Endocrinologia i Nutrició)
Pujol Borrell, Ricardo (Vall d'Hebron Hospitals. Institut de Recerca)
Verdaguer, Joan (Universitat de Lleida. Departament de Ciències Bàsiques)
Vives Pi, Marta (Hospital Germans Trias i Pujol)

Data: 2013
Resum: 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.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: T cells ; Apoptosis ; Gene expression ; Dendritic cells ; Cytokines ; Regulatory T cells ; Microarrays ; Diabetes mellitus
Publicat a: PLoS One, Vol. 8 Issue 5 (May 2013) , p. e63296, ISSN 1932-6203

DOI: 10.1371/journal.pone.0063296


10 p, 893.6 KB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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 Registre creat el 2015-10-20, darrera modificació el 2016-10-03



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