School of Clinical Laboratory Science, Guizhou Medical University, Guiyang 550000, Guizhou, China; Department of Clinical Laboratory, Minda Hospital affiliated Hubei Minzu University, Enshi 445000, Hubei, China.
Department of Microbiology and Immunology, Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou, China.
Int Immunopharmacol. 2021 Feb;91:107273. doi: 10.1016/j.intimp.2020.107273. Epub 2020 Dec 24.
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.
耐受性树突状细胞（tolDCs）是具有免疫抑制作用的细胞，作为免疫治疗工具，在类风湿关节炎（RA）中发挥重要作用。我们旨在研究同种异体 tolDCs（allo-tolDCs）和自体 tolDCs（auto-tolDCs）在体内是否具有长期的免疫耐受潜力，并改善胶原诱导关节炎（CIA）大鼠的关节炎。通过 NF-κB 诱饵 ODN 诱导 tolDCs，并通过流式细胞术负载牛Ⅱ型胶原（CII-loaded tolDCs）并进行鉴定，并用 DiR 标记后注入 CIA 大鼠。在不同时间点通过 IVIS 成像监测 DiR 标记的 tolDCs 的体内分布。收获主要器官并通过体外细胞成像进行分析。成功构建了 tolDCs，与 DCs 相比，其 CD80 和 CD86 的表达水平较低。所有 DiR（+）组的荧光信号至少观察到 25 天，最长观察到 35 天。注射后 DiR（+）CII-loaded allo-和 auto-tolDCs 主要分布在胸部和腹部，随着时间的推移逐渐转移到四肢关节。与未接受 tolDCs 治疗的 CIA 大鼠相比，allo-和 auto-tolDCs 降低了 CIA 大鼠中不同严重程度 IFN-γ和 IL-2 的表达，同时显著增加了 IL-4 和 IL-10 的表达。此外，这些 tolDCs 改善了 CIA 大鼠中不同严重程度的踝关节损伤。allo-和 auto-tolDCs 在体内均表现出长期的免疫耐受潜力，并改善了 CIA 大鼠中不同严重程度的关节炎。
