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Therapeutic Effect of Tolerogenic Dendritic Cells in Established Collagen-Induced Arthritis Is Associated With a Reduction in Th17 Responses

Lookup NU author(s): Dr Jeroen Stoop, Dr Rachel Harry, Dr Alexei von Delwig, Professor John Isaacs, Professor John Robinson, Dr Catharien Hilkens

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Abstract

Objective. Tolerogenic dendritic cells (DCs) are antigen-presenting cells with an immunosuppressive function. They are a promising immunotherapeutic tool for the attenuation of pathogenic T cell responses in autoimmune arthritis. The aims of this study were to determine the therapeutic action of tolerogenic DCs in a type II collagen-induced arthritis model and to investigate their effects on Th17 cells and other T cell subsets in mice with established arthritis. Methods. Tolerogenic DCs were generated by treating bone marrow-derived DCs with dexamethasone and vitamin D3 during lipopolysaccharide-induced maturation. Mice with established arthritis received 3 intravenous injections of tolerogenic DCs, mature DCs, or saline. Arthritis severity was monitored for up to 4 weeks after treatment. Fluorescence-labeled tolerogenic DCs were used for in vivo trafficking studies. The in vivo effect of tolerogenic DCs on splenic T cell populations was determined by intracellular cytokine staining and flow cytometry. Results. Tolerogenic DCs displayed a semi-mature phenotype, produced low levels of inflammatory cytokines, and exhibited low T cell stimulatory capacity. Upon intravenous injection into arthritic mice, tolerogenic DCs migrated to the spleen, liver, lung, feet, and draining lymph nodes. Treatment of arthritic mice with type II collagen-pulsed tolerogenic DCs, but not unpulsed tolerogenic DCs or mature DCs, significantly inhibited disease severity and progression. This improvement coincided with a significant decrease in the number of Th17 cells and an increase in the number of interleukin-10-producing CD4+ T cells, whereas tolerogenic DC treatment had no detectable effect on Th1 cells or interleukin-17-producing gamma/delta T cells. Conclusion. Treatment with type II collagen-pulsed tolerogenic DCs decreases the proportion of Th17 cells in arthritic mice and simultaneously reduces the severity and progression of arthritis.


Publication metadata

Author(s): Stoop JN, Harry RA, von Delwig A, Isaacs JD, Robinson JH, Hilkens CMU

Publication type: Article

Publication status: Published

Journal: Arthritis & Rheumatism

Year: 2010

Volume: 62

Issue: 12

Pages: 3656-3665

Print publication date: 01/12/2010

ISSN (print): 0004-3591

ISSN (electronic): 1529-0131

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/art.27756

DOI: 10.1002/art.27756


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