title: Efferocytosis promotes suppressive effects on dendritic cells through prostaglandin E2 production in the context of autoimmunity.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Immunology, Germans Trias i Pujol Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Irma
authors.initials: I
authors.lastname: Pujol-Autonell
authors.forename: Rosa-Maria
authors.initials: RM
authors.lastname: Ampudia
authors.forename: Raquel
authors.initials: R
authors.lastname: Planas
authors.forename: Silvia
authors.initials: S
authors.lastname: Marin-Gallen
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrascal
authors.forename: Alex
authors.initials: A
authors.lastname: Sanchez
authors.forename: Ana
authors.initials: A
authors.lastname: Marin
authors.forename: Manuel
authors.initials: M
authors.lastname: Puig-Domingo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pujol-Borrell
authors.forename: Joan
authors.initials: J
authors.lastname: Verdaguer
authors.forename: Marta
authors.initials: M
authors.lastname: Vives-Pi
mesh_terms: D000818:Animals; D015551:Autoimmunity; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D051379:Mice; D016688:Mice, Inbred NOD; D010587:Phagocytosis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
chemical_list: D015232:Dinoprostone