研究动态
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拉波尼特通过重新规划溶酶体来调控DC迁移,从而促进有效的抗病毒CD8+ T细胞应答,由此点燃钙电波。

Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer Dc Migration for An Effective Antiviral CD8+ T-Cell Response.

发表日期:2023 Aug 28
作者: Chenyan Li, Yangyang Hou, Minwei He, Liping Lv, Yulong Zhang, Sujing Sun, Yan Zhao, Xingzhao Liu, Ping Ma, Xiaohui Wang, Qianqian Zhou, Linsheng Zhan
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

以树突状细胞 (DC)-基于疫苗的免疫治疗是治疗癌症和传染病的一种成熟方法,但其疗效有限。因此,通过针对DC的有限迁移能力,可以增强其治疗效果。本研究评估了优灵土 (Lap) 对DC的影响,Lap可以被内化到溶酶体中,通过溶酶体重编程-钙闪烁轴诱导细胞骨架重组。研究发现,Lap显著改善了这些DC对淋巴组织的体内寻程能力。此外,Lap还改善了DC的抗原交叉呈递,并增加了DC-T细胞突触的形成,从而增强了特异性抗原CD8+ T细胞的活化。此外,基于黄金标准C-C的构建了一个Lap修饰的混合物 (Lap@细胞因子混合物 [C-C]) 作为DC疫苗的佐剂。Lap@C-C佐剂的DC启动了对乙型肝炎感染的强烈细胞毒性T细胞免疫应答,导致 > 99.6% 病毒DNA清除和乙型肝炎表面抗原血清学转化的成功。这些发现突显了Lap作为DC疫苗佐剂的潜在价值,它可以调控DC的寻程,并为开发有效的DC疫苗提供了基础。© 2023 The Authors. Advanced Science 由 Wiley-VCH GmbH 发布。
Immunotherapy using dendritic cell (DC)-based vaccination is an established approach for treating cancer and infectious diseases; however, its efficacy is limited. Therefore, targeting the restricted migratory capacity of the DCs may enhance their therapeutic efficacy. In this study, the effect of laponite (Lap) on DCs, which can be internalized into lysosomes and induce cytoskeletal reorganization via the lysosomal reprogramming-calcium flicker axis, is evaluated, and it is found that Lap dramatically improves the in vivo homing ability of these DCs to lymphoid tissues. In addition, Lap improves antigen cross-presentation by DCs and increases DC-T-cell synapse formation, resulting in enhanced antigen-specific CD8+ T-cell activation. Furthermore, a Lap-modified cocktail (Lap@cytokine cocktail [C-C]) is constructed based on the gold standard, C-C, as an adjuvant for DC vaccines. Lap@C-C-adjuvanted DCs initiated a robust cytotoxic T-cell immune response against hepatitis B infection, resulting in > 99.6% clearance of viral DNA and successful hepatitis B surface antigen seroconversion. These findings highlight the potential value of Lap as a DC vaccine adjuvant that can regulate DC homing, and provide a basis for the development of effective DC vaccines.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.