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Transcription profiling by array of mouse dendritic cells which were pulsed with apoptotic bodies from NIT-1 cells

ABSTRACT: We have been interested whether peripheral tolerance can be restored by vaccination with antigen-presenting cells (APCs) loaded with apoptotic bodies. Dendritic cells (DCs) are powerful APCs that have a critical role in the initiation and progression of autoimmunity. We previously demonstrated that DCs loaded with apoptotic islet cells prevents experimental type 1 diabetes (T1D), an autoimmune disease caused by beta-cell destruction. The goal of this study is to characterize the molecular changes on gene expression -transcriptome- occurring in these DCs pulsed with apoptotic bodies. Cells from four different genetically identical NOD (Non-Obese Diabetic) mice were used to obtain DCs. DCs were loaded with apoptotic bodies from NIT-1 cell line (insulinoma from NOD mice). Unloaded DCs were used as control in four paired experiments. Moreover, transcriptome from NIT-1 apoptotic bodies was determined. Mouse Gene 1.0 ST Arrays from Affymetrix (28,853 genes) were hybridized and genes with a p-value <= 0.002, adjusted p-value <= 0.08 and fold change (FC) >= 1.38 were considered upregulated, and genes with FC <= -1.37 were considered downregulated. Results demonstrate that apoptotic cells engulfment promotes molecular changes in DCs towards tolerogenic features. Gene expression profile of DCs from NOD mice that captured NIT-1 apoptotic bodies showed a downregulation of genes involved in antigen presentation and differential expression of cytokine, chemokine, natural immunity and immunoregulation genes together with the presence of specific transcripts for islet autoantigens. Molecular changes of DCs caused by the uptake of apoptotic bodies are key factors to induce antigen-specific peripheral tolerance.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Mus musculus  

DISEASE(S): Insulinoma,No Disease

SUBMITTER: Irma Pujol Autonell  

PROVIDER: E-MEXP-3374 | ArrayExpress | 2013-05-22


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Efferocytosis promotes suppressive effects on dendritic cells through prostaglandin E2 production in the context of autoimmunity.

Pujol-Autonell Irma I   Ampudia Rosa-Maria RM   Planas Raquel R   Marin-Gallen Silvia S   Carrascal Jorge J   Sanchez Alex A   Marin Ana A   Puig-Domingo Manuel M   Pujol-Borrell Ricardo R   Verdaguer Joan J   Vives-Pi Marta M  

PloS one 20130515 5

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-esta  ...[more]

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