Background/Purpose: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by synovial inflammation, cartilage breakdown and bone destruction with the involvement of various types of cells including dendritic cells (DCs). A subset of dendritic cells that induce tolerance is called tolerogenic DCs (tolDCs). They may represent a promising immunosuppressive therapeutic tool for the attenuation of pathogenic T cell responses in autoimmune arthritis. In this study, we examine a series of stable antigen-specific tolDCs with tracking green fluorescent protein (GFP) to investigate their influence in the murine collagen induced arthritis (CIA) model.

Methods: The DCs were isolated from bone marrow of DBA/1Lac/J mice, and stimulated with IL-10 (10ng/ml), TGF-β (10ng/ml), and type II Collagen (CII) to induce CII-specific tolerogenic dendritic cells (tolDCs). The cells were then infected with Lenti-GFP viral vectors for GFP transduction. The GFP-tolDCs were injected ip into CIA mice at the time of arthritis onset. Arthritic animals were clinically assessed 3 times a week. The arthritic paws and blood specimens were harvested at 8 weeks after onset for histological, immunological and molecular analyses.

Results: The phenotype of tolDCs was confirmed by flow cytometry and ELISA.  Lymphocyte proliferation assays resulted in semi-matured, high IL-10 and TGF-β production, and low lymphocyte stimulatory capacity with low IFN-γ secretion. Both clinical and histological assessment on the animal studies indicated that the mice receiving tolDCs transfusion had a rapid and significant reduction in severity of arthritis compared to the controls (P<0.01). Fluorescent microscope observation showed aggregated green fluorescent cells in the inflamed synovial membrane where only sporadic presence in liver, spleen or lungs. Data also indicated the extended high expression levels of IL-10 and TGF-β at 4 weeks after the treatment, whereas the IL-17 expression was lower than controls (P < 0.01).

Conclusion: This study reports the successful establishment of a stable phenotype of CII-specific tolDCs and its potential therapeutic influence on collagen-induced arthritis in mice. Introduction of GFP-tolDCs significantly ameliorates the clinical and pathological progress of the experimental arthritis. TolDCs were cumulative at the inflammatory joints and the treatment diminished Th17 response (IL-17 expression). Further investigation is due to reveal the mechanism of tolDCs in regulation of the progression of rheumatoid arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tolerogenic-dendritic-cells-ameliorates-the-disease-severity-of-murine-collagen-induced-arthritis/