调节性成纤维细胞样滑膜细胞细胞膜包被的纳米颗粒：类风湿关节炎的新型靶向治疗,Advanced Science

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调节性成纤维细胞样滑膜细胞细胞膜包被的纳米颗粒：类风湿关节炎的新型靶向治疗
Advanced Science ( IF 14.3 ) Pub Date : 2022-12-12 , DOI: 10.1002/advs.202204998
Yuan Liu _{1,

2,

3} , Peishi Rao _{1,

2,

4} , Hongyan Qian _{1,

2,

3} , Yesi Shi ₅ , Shiju Chen _{1,

2,

3} , Jingying Lan _{1,

2} , Dan Mu ₅ , Rongjuan Chen _{1,

2} , Xinwei Zhang _{1,

2,

3} , Chaoqiong Deng _{1,

2} , Gang Liu ₅ , Guixiu Shi _{1,

2,

3}

Affiliation

成纤维细胞样滑膜细胞（FLS）是类风湿性关节炎（RA）患者发炎关节中的主要细胞成分。FLS 与浸润性 T 细胞密切相互作用。成纤维细胞对 T 细胞具有有效的抑制作用，从而解决炎症和免疫耐受。然而，这种“调节”表型在 RA 中存在缺陷，而 RA 中的 FLS 相反充当介导炎症持续的“促炎”表型。协调成纤维细胞异质性的信号仍不清楚。在这里，证明不同的细胞因子可以诱导不同的 FLS 表型。干扰素-γ (IFN- γ ) 在诱导 FLS 调节表型（称为 FLS ^reg）方面发挥着关键作用，其特征是多种抑制分子的高表达。雷帕霉素增强 IFN- γ对 FLS的作用。基于FLS ^{reg的特性，通过将IFN-}γ和雷帕霉素诱导的FLS ^reg衍生的细胞膜涂覆在纳米粒子上，设计了一种新的RA仿生治疗策略，称为FIRN。FIRN 在 RA 小鼠模型中表现出良好的疗效、稳定性和炎症关节靶向能力。这些发现阐明了成纤维细胞表型如何在炎症微环境中受到调节，并为基于调节成纤维细胞的自身免疫性疾病的新型治疗设计提供了见解。

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Regulatory Fibroblast-Like Synoviocytes Cell Membrane Coated Nanoparticles: A Novel Targeted Therapy for Rheumatoid Arthritis

Fibroblast-like synoviocytes (FLS) are the main cell component in the inflamed joints of patients with rheumatoid arthritis (RA). FLS intimately interact with infiltrating T cells. Fibroblasts have potent inhibitory effects on T cells, leading to the resolution of inflammation and immune tolerance. However, this “regulatory” phenotype is defect in RA, and FLS in RA instead act as “proinflammatory” phenotype mediating inflammation perpetuation. Signals that orchestrate fibroblast heterogeneity remain unclear. Here, it is demonstrated that different cytokines can induce distinct phenotypes of FLS. Interferon-gamma (IFN-γ) is pivotal in inducing the regulatory phenotype of FLS (which is termed FLS^reg) characterized by high expressions of several inhibitory molecules. Rapamycin enhances the effect of IFN-γ on FLS. Based on the characteristics of FLS^reg, a novel biomimetic therapeutic strategy for RA is designed by coating cell membrane derived from FLS^reg induced by IFN-γ and rapamycin on nanoparticles, which is called FIRN. FIRN show good efficacy, stability, and inflammatory joint targeting ability in an RA mouse model. The findings clarify how fibroblast phenotypes are modulated in the inflammatory microenvironment and provide insights into novel therapeutic designs for autoimmune diseases based on regulatory fibroblasts.

更新日期：2022-12-12

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