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

Cellular & Molecular Immunology volume 16, pages 791–799 (2019)Cite this article

Abstract

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.

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Acknowledgements

We thank Linda Oberdörfer, Kerstin Daemen, and Jana Keil for excellent technical assistance and Svetlana Piter for excellent animal care. This work was supported by Deutsche Forschungsgemeinschaft (DFG) grant KFO 250-FO 334/2-1 to R. Förster.

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Author notes

  1. Elisabeth Kremmer

    Present address: Biozentrum Martinsried, Dept. Bio II., LMU München, Grosshaderner Str. 2, D-82152, Martinsried, Germany

Authors and Affiliations

  1. Institute of Immunology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany

    Georgios L. Moschovakis, Anja Bubke, Michaela Friedrichsen, Jasmin Ristenpart & Reinhold Förster

  2. Pepscan Therapeutics BV, Lelystad, The Netherlands

    Jaap Willem Back

  3. Institute of Transplant Immunology, Integrated Research and Treatment Center Transplantation, IFB.Tx, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany

    Christine S. Falk

  4. Helmholtz-Zentrum München, Institute of Molecular Immunology, D-81377, Munich, Germany

    Elisabeth Kremmer

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Contributions

G.L.M., A.B., M.F., and J.R. performed experiments; G.L.M. and C.S.F. analyzed experiments; J.W.B. and E.K. provided essential reagents for the study; G.L.M. and R.F. designed experiments and wrote the paper. The manuscript was approved by all authors.

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Correspondence to Georgios L. Moschovakis or Reinhold Förster.

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Competing interests

G.L.M., A.B., M.F., J.R., C.S.F., E.K., and R.F. declare no conflicts of interest. J.W.B. is an employee of Pepscan and was named inventor on a patent disclosing anti-CCR7 antibodies.

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Moschovakis, G.L., Bubke, A., Friedrichsen, M. et al. The chemokine receptor CCR7 is a promising target for rheumatoid arthritis therapy. Cell Mol Immunol 16, 791–799 (2019). https://doi.org/10.1038/s41423-018-0056-5

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