The chemokine receptor CCR7 is a promising target for rheumatoid arthritis therapy

被引：46

作者：

Moschovakis, Georgios L. ^{[1
]}

Bubke, Anja ^{[1
]}

Friedrichsen, Michaela ^{[1
]}

Ristenpart, Jasmin ^{[1
]}

Back, Jaap Willem ^{[2
]}

Falk, Christine S. ^{[3
]}

Kremmer, Elisabeth ^{[4
,5
]}

Foerster, Reinhold ^{[1
]}

机构：

[1] Hannover Med Sch, Inst Immunol, Carl Neuberg Str 1, D-30625 Hannover, Germany

[2] Pepscan Therapeut BV, Lelystad, Netherlands

[3] Hannover Med Sch, IFB Tx, Integrated Res & Treatment Ctr Transplantat, Inst Transplant Immunol, Carl Neuberg Str 1, D-30625 Hannover, Germany

[4] Helmholtz Zentrum Munchen, Inst Mol Immunol, Munich, Germany

[5] LMU Munchen, Dept Bio 2, Biozentrum Martinsried, Grosshaderner Str 2, D-82152 Martinsried, Germany

来源：

CELLULAR & MOLECULAR IMMUNOLOGY | 2019年 / 16卷 / 10期

关键词：

COLLAGEN-INDUCED ARTHRITIS; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; CUTTING EDGE; EXPRESSION; ANTI-CD3; DISEASE; CCL21; CCL19;

D O I：

10.1038/s41423-018-0056-5

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The chemokine receptor CCR7 and its ligands CCL19 and CCL21 guide the homing and positioning of dendritic and T cells in lymphoid organs, thereby contributing to several aspects of adaptive immunity and immune tolerance. In the present study, we investigated the role of CCR7 in the pathogenesis of collagen-induced arthritis (CIA). By using a novel anti-human CCR7 antibody and humanized CCR7 mice, we evaluated CCR7 as a target in this autoimmune model of rheumatoid arthritis (RA). Ccr7-deficient mice were completely resistant to CIA and presented severely impaired antibody responses to collagen II (CII). Selective CCR7 expression on dendritic cells restored arthritis severity and anti-CII antibody titers. Prophylactic and therapeutic treatment of humanized CCR7 mice with anti-human CCR7 mAb 8H3-16A12 led to complete resistance to CIA and halted CIA progression, respectively. Our data demonstrate that CCR7 signaling is essential for the induction of CIA and identify CCR7 as a potential therapeutic target in RA.

引用

页码：791 / 799

页数：9

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