Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), Newcastle upon Tyne, United Kingdom.
Front Immunol. 2022 Oct 3;13:988667. doi: 10.3389/fimmu.2022.988667. eCollection 2022.
Tolerogenic dendritic cell (tolDC) therapies aim to restore self-tolerance in patients suffering from autoimmune diseases. Phase 1 clinical trials with tolDC have shown the feasibility and safety of this approach, but have also highlighted a lack of understanding of their distribution . Fluorine-19 magnetic resonance imaging (F-MRI) promises an attractive cell tracking method because it allows for detection of F-labelled cells in a non-invasive and longitudinal manner. Here, we tested the suitability of nanoparticles containing F (F-NP) for labelling of therapeutic human tolDC for detection by F-MRI. We found that tolDC readily endocytosed F-NP with acceptable effects on cell viability and yield. The MRI signal-to-noise ratios obtained are more than sufficient for detection of the administered tolDC dose (10 million cells) at the injection site , depending on the tissue depth and the rate of cell dispersal. Importantly, F-NP labelling did not revert tolDC into immunogenic DC, as confirmed by their low expression of typical mature DC surface markers (CD83, CD86), low secretion of pro-inflammatory IL-12p70, and low capacity to induce IFN-γ in allogeneic CD4 T cells. In addition, the capacity of tolDC to secrete anti-inflammatory IL-10 was not diminished by F-NP labelling. We conclude that F-NP is a suitable imaging agent for tolDC. With currently available technologies, this imaging approach does not yet approach the sensitivity required to detect small numbers of migrating cells, but could have important utility for determining the accuracy of injecting tolDC into the desired target tissue and their efflux rate.
免疫耐受树突状细胞(tolDC)疗法旨在恢复自身免疫性疾病患者的自身耐受性。tolDC 的 1 期临床试验已经证明了这种方法的可行性和安全性,但也突出了对其分布的理解不足。氟-19 磁共振成像(F-MRI)有望成为一种有吸引力的细胞追踪方法,因为它可以非侵入性地、纵向地检测到 F 标记的细胞。在这里,我们测试了含氟纳米颗粒(F-NP)标记治疗性人 tolDC 的适用性,以便通过 F-MRI 进行检测。我们发现 tolDC 可以很好地内吞 F-NP,对细胞活力和产量的影响可以接受。获得的 MRI 信噪比足以检测到注射部位的给药 tolDC 剂量(1000 万个细胞),这取决于组织深度和细胞分散速度。重要的是,F-NP 标记不会使 tolDC 转变为免疫原性 DC,这一点得到了证实,因为它们表面标志物(CD83、CD86)的典型成熟 DC 的低表达、促炎细胞因子 IL-12p70 的低分泌以及对同种异体 CD4 T 细胞 IFN-γ的低诱导能力。此外,F-NP 标记不会降低 tolDC 分泌抗炎性细胞因子 IL-10 的能力。我们得出结论,F-NP 是 tolDC 的一种合适的成像剂。使用当前可用的技术,这种成像方法还没有达到检测迁移细胞的所需灵敏度,但对于确定将 tolDC 准确注入所需靶组织以及它们的流出率具有重要的实用价值。
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