In multiple sclerosis (MS), abnormally activated immune cells responsive to myelin proteins result in widespread damage throughout the central nervous system (CNS) and ultimately irreversible disability. Immunomodulation by delivering dendritic cells (DCs) utilizes a potent and rapid MS disease progression driver therapeutically. Here, we investigated delivering DCs for disease severity attenuation using an experimental autoimmune encephalomyelitis preclinical MS model. DCs treated with interleukin‐10 (IL‐10) (DC10s) were transplanted using in situ gelling poly(ethylene glycol)‐based hydrogel for target site localization. DC delivery increased hydrogel longevity and altered the injection site recruited, endogenous immune cell profile within 2 days postinjection. Furthermore, hydrogel‐mediated DC transplantation efficacy depended on the injection‐site. DCs delivered to the neck local to MS‐associated CNS‐draining cervical lymph nodes attenuated paralysis, compared to untreated controls, while delivery to the flank did not alter paralysis severity. This study demonstrates that local delivery of DC10s modulates immune cell recruitment and attenuates disease progression in a preclinical model of MS.

中文翻译：

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局部水凝胶递送树突状细胞以减轻小鼠模型中的多发性硬化症


在多发性硬化症 (MS) 中，对髓磷脂蛋白作出反应的异常激活的免疫细胞会导致整个中枢神经系统 (CNS) 广泛受损，并最终导致不可逆转的残疾。通过递送树突状细胞 (DC) 进行免疫调节在治疗上利用了有效且快速的多发性硬化症疾病进展驱动因素。在这里，我们使用实验性自身免疫性脑脊髓炎临床前 MS 模型研究了递送 DC 以减轻疾病严重程度。使用原位胶凝聚乙二醇水凝胶移植经白细胞介素 10 (IL-10) (DC10s) 处理的 DC，以进行靶位点定位。 DC 递送延长了水凝胶的寿命，并在注射后 2 天内改变了注射部位招募的内源性免疫细胞特征。此外，水凝胶介导的 DC 移植功效取决于注射部位。与未经治疗的对照相比，将 DC 递送至颈部局部 MS 相关中枢神经系统引流颈部淋巴结可减轻麻痹，而递送至侧腹并不会改变麻痹的严重程度。这项研究表明，在多发性硬化症临床前模型中，DC10 的局部递送可调节免疫细胞募集并减弱疾病进展。