Apoptotic cell infusion treats ongoing collagen-induced arthritis, even in the presence of methotrexate, and is synergic with anti-TNF therapy

Abstract : AbstractBackgroundApoptotic 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.MethodsThe 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.ResultsTreatment 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.ConclusionOverall, 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.
Type de document :
Article dans une revue
Arthritis Research and Therapy, BioMed Central, 2015, 18 (1), pp.184. 〈10.1186/s13075-016-1084-0〉
Liste complète des métadonnées

Littérature citée [37 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01353517
Contributeur : Bmc Bmc <>
Soumis le : jeudi 11 août 2016 - 18:03:06
Dernière modification le : jeudi 15 mars 2018 - 10:02:06
Document(s) archivé(s) le : samedi 12 novembre 2016 - 12:29:40

Fichier

13075_2016_Article_1084.pdf
Publication financée par une institution

Identifiants

Collections

Citation

Francis Bonnefoy, Anna Daoui, Séverine Valmary-Degano, Eric Toussirot, Philippe Saas, et al.. Apoptotic cell infusion treats ongoing collagen-induced arthritis, even in the presence of methotrexate, and is synergic with anti-TNF therapy. Arthritis Research and Therapy, BioMed Central, 2015, 18 (1), pp.184. 〈10.1186/s13075-016-1084-0〉. 〈inserm-01353517〉

Partager

Métriques

Consultations de la notice

69

Téléchargements de fichiers

47