脂质纳米颗粒作为剖析树突状细胞成熟途径的工具。
Lipid nanoparticles as a tool to dissect dendritic cell maturation pathways.
作者信息
Rennen Sofie, Bosteels Victor, De Nolf Clint, Maréchal Sandra, Vetters Jessica, Van Lil Karo, Webb Greta, Swinnen Janne, Van De Velde Evelien, Fayazpour Farzaneh, Roelandt Ria, Vandamme Niels, Verstaen Kevin, De Smedt Stefaan C, Breckpot Karine, Vanhee Stijn, Gevaert Philippe, Hoste Eric, De Geest Bruno G, Verbeke Rein, Lentacker Ine, Janssens Sophie
机构信息
Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Laboratory for Barriers in Inflammation, VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
出版信息
Cell Rep. 2025 Aug 26;44(8):116150. doi: 10.1016/j.celrep.2025.116150. Epub 2025 Aug 18.
Depending on how antigens are being decoded by dendritic cells (DCs), their acquisition will induce a homeostatic or immunogenic maturation program. This determines how antigens are being presented and whether DCs instruct T cells to induce tolerance or immunity. So far, the field lacks proper tools to distinguish the two maturation states. By using a lipid nanoparticle (LNP)-based approach and cellular indexing of transcriptomes and epitopes sequencing analysis, we designed a flow cytometry panel and transcriptional profiling tools to reliably annotate the two DC maturation states. The data corroborate that uptake of empty (or peptide-containing) LNPs induces homeostatic maturation in DCs, while uptake of Toll-like receptor ligand-adjuvanted (or mRNA-containing) LNPs induces immunogenic maturation, yielding distinct T cell outputs. This reveals that LNPs are not decoded as "dangerous" by DCs, and that the cargo is essential to provide adjuvant activity, which is highly relevant for the targeted design of LNP-based therapies.
根据树突状细胞（DCs）对抗原的解码方式，其摄取将诱导稳态或免疫原性成熟程序。这决定了抗原的呈递方式以及DCs是否指导T细胞诱导耐受或免疫。到目前为止，该领域缺乏区分这两种成熟状态的合适工具。通过使用基于脂质纳米颗粒（LNP）的方法以及转录组和表位测序分析的细胞索引，我们设计了一种流式细胞术面板和转录谱分析工具，以可靠地注释两种DC成熟状态。数据证实，摄取空的（或含肽的）LNP会诱导DCs的稳态成熟，而摄取 Toll样受体配体佐剂（或含mRNA的）LNP会诱导免疫原性成熟，产生不同的T细胞输出。这表明DCs不会将LNP解码为“危险”物质，并且货物对于提供佐剂活性至关重要，这与基于LNP的疗法的靶向设计高度相关。
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