Efferocytosis promotes suppressive effects on dendritic cells through prostaglandin E2 production in the context of autoimmunity
Ampudia, Rosa Maria
Vives Pi, Marta
MetadataShow full item record
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.
Is part ofPLoS One, 2013, vol. 8, núm. 5, e63296
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as cc-by, (c) Pujol-Autonell et al., 2013
Showing items related by title, author, creator and subject.
Pujol Autonell, Irma; Serracant Prat, Arnau; Cano Sarabia, Antonia María; Ampudia, Rosa Maria; Rodríguez Fernández, Silvia; Sánchez (Sànchez Pla), Álex; Izquierdo, Cristina; Stratmann, Thomas; Puig-Domingo, Manuel; Maspoch, Daniel; Verdaguer Autonell, Joan; Vives Pi, Marta (Public Library Science, 2015-06-03)
Phosphatidylserine-liposomes Promote Tolerogenic Features on Dendritic cells in human Type 1 Diabetes by apoptotic Mimicry Rodríguez Fernández, Silvia; Pujol Autonell, Irma; Briansó Castilla, Ferran; Perna Barrull, David; Cano Sarabia, Antonia María; García Jimeno, Sonia; Villalba, Adrian; Sánchez (Sànchez Pla), Álex; Aguilera, Eva; Vázquez San Miguel, Federico; Verdaguer Autonell, Joan; Maspoch, Daniel; Vives Pi, Marta (Frontiers Media, 2018)Type 1 diabetes (T1D) is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow ...
B-cell anergy induces a Th17 shift in a novel B lymphocyte transgenic NOD mouse model, the 116C-NOD mouse Carrascal, Jorge; Carrillo, Jorge; Arpa i Puigdemont, Berta; Egia-Mendikute, Leire; Rosell Mases, Estela; Pujol Autonell, Irma; Planas, Raquel; Mora Giral, Concepció; Mauricio Puente, Dídac; Ampudia, Rosa Maria; Vives Pi, Marta; Verdaguer Autonell, Joan (Wiley online library, 2016)Autoreactive B lymphocytes play a key role as APCs in diaebetogenesis. However, it remains unclear whether B-cell tolerance is compromised in NOD mice. Here, we describe a new B lymphocyte transgenic NOD mouse model, the ...