Immunotherapy with dendritic cells in a humanised mouse model of rheumatoid arthritis

我们的目标是开发一种使用一种名为树突状细胞(DC)的免疫细胞来治疗类风湿关节炎(RA)的新疗法。类风湿关节炎是一种疼痛的疾病，会导致手、脚和四肢的关节僵硬和畸形。在英国，近40万人患有类风湿性关节炎。目前还没有治愈这种疾病的方法。类风湿性关节炎是由患者自身的免疫系统引起的：白细胞错误地攻击关节，导致软骨和骨骼的破坏。我们已经制造了一种特殊类型的DC，能够防止白细胞攻击关节(即使血细胞‘耐受’)，并希望这种DC可以用于治疗RA。这种类型的DC被称为耐受性DC(TolDC)。我们的工作解决了在我们可以在人类身上测试TolDC治疗之前必须回答的重要问题。例如，我们需要知道需要多少TolDC来抑制关节炎；必须在哪里注射它们(例如，在血液中、关节中)；它们能在体内存活多长时间；它们如何使白细胞耐受。我们将用发展成类似RA的疾病的小鼠来解决这些问题。如果成功，我们的工作将带来一种新的、有望有益的RA治疗方法，更接近临床应用。

We aim to develop a new therapy for rheumatoid arthritis (RA) using a type of immune cell called a dendritic cell (DC). RA is a painful disease that leads to stiffness and deformity of joints in hands, feet and limbs. Almost 400,000 people in the UK suffer from RA. No cure for this disease is available yet.RA is caused by a patient’s own immune system: white blood cells mistakenly attack joints and cause destruction of cartilage and bone. We have made a special type of DC with the ability to prevent white blood cells attacking the joint (i.e. make the blood cells ‘tolerant’) and hope this can be used to treat RA. This type of DC is called tolerogenic DC (tolDC).Our work addresses important questions that must be answered before we can test tolDC treatment in humans. For instance, we need to know how many tolDC will be required to inhibit arthritis; where they will have to be injected (e.g. in the blood, in the joint); how long they will survive in the body; and how they make white blood cells tolerant. We will address these questions using mice which develop a disease similar to RA.If successful, our work will bring a new and hopefully beneficial treatment for RA closer to clinical use.