title: Apoptotic cell infusion treats ongoing collagen-induced arthritis, even in the presence of methotrexate, and is synergic with anti-TNF therapy.
abstract: Apoptotic cell-based therapies have been proposed to treat chronic inflammatory diseases. The aim of this study was to investigate the effect of intravenous (i.v.) apoptotic cell infusion in ongoing collagen-induced arthritis (CIA) and the interaction of this therapy with other treatments used in rheumatoid arthritis (RA), including methotrexate (MTX) or anti-TNF therapy.
  
  
  
  The effects of i.v. apoptotic cell infusion were evaluated in a CIA mouse model in DBA/1 mice immunized with bovine type II collagen. The number and functions of antigen-presenting cells (APC), regulatory CD4(+) T cells (Treg), and circulating anti-collagen auto-antibodies were analyzed in CIA mice.
  
  
  
  Treatment of arthritic mice with i.v. apoptotic cell infusion significantly reduced the arthritis clinical score. This therapeutic approach modified T cell responses against the collagen auto-antigen with selective induction of collagen-specific Treg. In addition, we observed that APC from apoptotic-cell-treated animals were resistant to toll-like receptor ligand activation and favored ex vivo Treg induction, indicating APC reprogramming. Apoptotic cell injection-induced arthritis modulation was dependent on transforming growth factor (TGF)-β, as neutralizing anti-TGF-β antibody prevented the effects of apoptotic cells. Methotrexate did not interfere, while anti-TNF therapy was synergic with apoptotic-cell-based therapy.
  
  
  
  Overall, our data demonstrate that apoptotic-cell-based therapy is efficient in treating ongoing CIA, compatible with current RA treatments, and needs to be evaluated in humans in the treatment of RA.
authors: INSERM UMR1098, F-25000, Besançon, France.|Université de Bourgogne Franche-Comté, SFR FED4234, F-25000, Besançon, France.|EFS Bourgogne Franche-Comté, F-25000, Besançon, France.|LabEX LipSTIC, ANR-11-LABX-0021, F-25000, Besançon, France.|FHU INCREASE, Besançon University Hospital, F-25000, Besançon, France.
authors: Francis
authors: F
authors: Bonnefoy
authors: INSERM UMR1098, F-25000, Besançon, France.|Université de Bourgogne Franche-Comté, SFR FED4234, F-25000, Besançon, France.|EFS Bourgogne Franche-Comté, F-25000, Besançon, France.|LabEX LipSTIC, ANR-11-LABX-0021, F-25000, Besançon, France.|FHU INCREASE, Besançon University Hospital, F-25000, Besançon, France.
authors: Anna
authors: A
authors: Daoui
authors: Pathology Department, Besancon University Hospital, F-25000, Besançon, France.
authors: Séverine
authors: S
authors: Valmary-Degano
authors: LabEX LipSTIC, ANR-11-LABX-0021, F-25000, Besançon, France.|FHU INCREASE, Besançon University Hospital, F-25000, Besançon, France.|INSERM CIC1431, Clinical Investigation Center Biotherapy, Besançon University Hospital, F-25000, Besançon, France.|Rheumatology Department, Besançon University Hospital, F-25000, Besançon, France.
authors: Eric
authors: E
authors: Toussirot
authors: INSERM UMR1098, F-25000, Besançon, France.|Université de Bourgogne Franche-Comté, SFR FED4234, F-25000, Besançon, France.|EFS Bourgogne Franche-Comté, F-25000, Besançon, France.|LabEX LipSTIC, ANR-11-LABX-0021, F-25000, Besançon, France.|FHU INCREASE, Besançon University Hospital, F-25000, Besançon, France.|INSERM CIC1431, Clinical Investigation Center Biotherapy, Besançon University Hospital, F-25000, Besançon, France.
authors: Philippe
authors: P
authors: Saas
authors: INSERM UMR1098, F-25000, Besançon, France. sylvain.perruche@inserm.fr.|Université de Bourgogne Franche-Comté, SFR FED4234, F-25000, Besançon, France. sylvain.perruche@inserm.fr.|EFS Bourgogne Franche-Comté, F-25000, Besançon, France. sylvain.perruche@inserm.fr.|LabEX LipSTIC, ANR-11-LABX-0021, F-25000, Besançon, France. sylvain.perruche@inserm.fr.|FHU INCREASE, Besançon University Hospital, F-25000, Besançon, France. sylvain.perruche@inserm.fr.|UMR1098 INSERM, Etablissement Français du Sang de BFC, 8 Rue du Dr JFX Girod, F-25000, Besançon, France. sylvain.perruche@inserm.fr.
authors: Sylvain
authors: S
authors: Perruche
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005260:Female; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D060168:Thymocytes / Q000637:transplantation*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate