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

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 c...

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Bibliographic Details
Published in:Cellular & molecular immunology 2019-10, Vol.16 (10), p.791-799
Main Authors: Moschovakis, Georgios L., Bubke, Anja, Friedrichsen, Michaela, Ristenpart, Jasmin, Back, Jaap Willem, Falk, Christine S., Kremmer, Elisabeth, Förster, Reinhold
Format: Article
Language:English
Subjects:
Adaptive immunity
Animals
Antibodies
Antibodies, Monoclonal - metabolism
Arthritis, Experimental - metabolism
Arthritis, Rheumatoid - metabolism
Autoantibodies - metabolism
Biomedical and Life Sciences
Biomedicine
CC chemokine receptors
CCL19 protein
CCL21 protein
CCR7 protein
Chemokines
Collagen (type II)
Collagen Type II - immunology
Dendritic cells
Dendritic Cells - immunology
Disease Progression
Disease Resistance
Humans
Immunological tolerance
Immunology
Lymphocytes T
Medical Microbiology
Mice
Mice, Knockout
Microbiology
Molecular Targeted Therapy
Monoclonal antibodies
Receptors, CCR7 - genetics
Receptors, CCR7 - immunology
Receptors, CCR7 - metabolism
Rheumatoid arthritis
Therapeutic applications
Vaccine
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Summary: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.
ISSN:1672-7681
2042-0226
DOI:10.1038/s41423-018-0056-5