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

被引：32

作者：

Bonnefoy, Francis ^{[1
,2
,3
,4
,5
]}

Daoui, Anna ^{[1
,2
,3
,4
,5
]}

Valmary-Degano, Severine ^{[6
]}

Toussirot, Eric ^{[7
,8
]}

Saas, Philippe ^{[1
,2
,3
,4
,5
,7
]}

Perruche, Sylvain ^{[1
,2
,3
,4
,5
,9
]}

机构：

[1] INSERM, UMR1098, F-25000 Besancon, France

[2] Univ Bourgogne Franche Comte, SFR FED4234, F-25000 Besancon, France

[3] EFS Bourgogne Franche Comte, F-25000 Besancon, France

[4] LabEX LipSTIC, ANR LABX 0021 11, F-25000 Besancon, France

[5] Besancon Univ Hosp, FHU INCREASE, F-25000 Besancon, France

[6] Besancon Univ Hosp, Dept Pathol, F-25000 Besancon, France

[7] Besancon Univ Hosp, Clin Invest Ctr Biotherapy, INSERM CIC1431, F-25000 Besancon, France

[8] Besancon Univ Hosp, Dept Rheumatol, F-25000 Besancon, France

[9] INSERM, UMR1098, Etab Francais Sang BFC, 8 Rue Dr JFX Girod, F-25000 Besancon, France

来源：

ARTHRITIS RESEARCH & THERAPY | 2016年 / 18卷

关键词：

REGULATORY T-CELLS; TGF-BETA; RHEUMATOID-ARTHRITIS; SUPPRESSIVE ACTIVITY; ADOPTIVE TRANSFER; PROTECT MICE; DISEASE; INDUCTION; TRANSPLANTATION; INFLAMMATION;

D O I：

10.1186/s13075-016-1084-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: 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. Methods: 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. Results: 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)-beta, as neutralizing anti-TGF-beta antibody prevented the effects of apoptotic cells. Methotrexate did not interfere, while anti-TNF therapy was synergic with apoptotic-cell-based therapy. Conclusion: 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.

引用

页数：13

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