DiR-labeled tolerogenic dendritic cells for targeted imaging in collagen- induced arthritis rats

Tolerogenic dendritic cells (tolDCs) are immunosuppressive cells and play an important role in rheumatoid arthritis (RA) as immunotherapeutic tools. We aimed to investigate whether allogeneic tolDCs (allo-tolDCs) and autologous tolDCs (auto-tolDCs) had long-time tolerogenic potential in vivo and improve arthritis in collagen-induced arthritis (CIA) rats. TolDCs were induced by NF-κB Decoy ODN, and loaded with Bovine Type II collagen (CII- loaded tolDCs) and identified by flow cytometry, and labeled with DiR and injected into CIA rats. The biodistribution of DiR-labeled tolDCs was monitored by IVIS imaging at different time points. Major organs were harvested and analyzed by ex-in vivo cell imaging. The tolDCs were successfully constructed, along with expressing low levels of CD80 and CD86 compared to DCs. The fluorescent signals of all DiR (+) groups were observed at least 25 days, and as long as 35 days. DiR (+) CII- loaded allo-and auto-tolDCs at post injection mainly distributed in the chest and abdomen and gradually moved to limb joints over time. The allo- and auto-tolDCs decreased the expression of IFN-γ and IL-2 in CIA rats with different severity compared to CIA rats without tolDCs treatment, while significantly increased the expression of IL-4 and IL-10. Additionally, these tolDCs ameliorated the ankle joints injury in CIA rats with different severity. The both allo- and auto-tolDCs showed long-time tolerogenic potential in vivo and ameliorated arthritis in CIA rats with different severity.