E-MEXP-3374 - Transcription profiling by array of mouse dendritic cells which were pulsed with apoptotic bodies from NIT-1 cells
Last updated on 21 May 2013, released on 22 May 2013
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.
transcription profiling by array, cell type comparison, co-expression, differentiation, ex vivo
Efferocytosis promotes suppressive effects on dendritic cells through prostaglandin E2 production in the context of autoimmunity. Irma Pujol-Autonell, Rosa-Maria Ampudia, Raquel Planas, Silvia Marin-Gallen, Jorge Carrascal, Alex Sanchez, Ana Marin, Manuel Puig-Domingo, Ricardo Pujol-Borrell, Joan Verdaguer, Marta Vives-Pi. PLOS ONE
Efferocytosis promotes suppressive effects on dendritic cells through prostaglandin E2 production in the context of autoimmunity. Pujol-Autonell I, Ampudia RM, Planas R, Marin-Gallen S, Carrascal J, Sanchez A, Marin A, Puig-Domingo M, Pujol-Borrell R, Verdaguer J, Vives-Pi M. :e63296 (2013), Europe PMC 23691013