Browse by author
Lookup NU author(s): Dr Jeroen Stoop, Dr Rachel Harry, Dr Alexei von Delwig, Professor John IsaacsORCiD, Professor John Robinson, Professor Catharien Hilkens
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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.
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
Altmetrics provided by Altmetric