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通过全身和粘膜导向的细胞因子治疗来招募和激活髓状细胞

Cordelia Manickam^1,2, Rhianna Jones¹, Nihar R Deb Adhikary³

¹Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Duke University School of Medicine, Durham, NC, USA.

Immunology and cell biology

|October 7, 2025

概括

皮下花细胞-巨细胞殖民地刺激因子 (GM-CSF) 有效地调动 rhesus 的髓状细胞,增强免疫反应,没有不良影响. 这项研究详细介绍了免疫细胞扩张的时间和位置,用于治疗应用.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
药理学药理学是指药理学的学科.

背景情况:

骨髓状细胞是抗体介导免疫中的关键Fc效应细胞.
颗粒细胞-巨细胞殖民地刺激因子 (GM-CSF) 是一种激活髓状细胞的细胞因子,用于各种治疗.
rhesus macaques (RM) 是疫苗和治疗开发的相关模型,因为可访问的粘膜采样.

研究的目的:

在RM中比较皮下 (subQ) 和局部的GM-CSF给药,以检测免疫细胞扩张和结果.
评估免疫细胞调动和激活的动力学.
评估GM-CSF的安全性和临床影响.

主要方法:

皮下和局部的GM-CSF被给予RM.
血液和粘膜组织 (直肠,阴道) 样本被纵向采集.
分析了免疫细胞群 (中性粒细胞,乙素细胞,单细胞),Fc受体表达 (CD64,CD32) 和细胞因子水平.
在组织活检上进行了组织学评估.

主要成果:

在1-3天内,SubQ GM-CSF的使用导致中性粒细胞,乙氨基粒细胞和单细胞的快速增加.
在血液中,分别在第7天和第8天观察到高素和中性素水平的峰值.
结直肠活检显示中性粒细胞,乙素粒细胞,CD64+和CD32+细胞的增加,表明Fc效应细胞的积累.
SubQ GM-CSF诱导了髓质细胞激活和贩运,由增加的细胞因子水平 (CXCL13,MCP-1,IL-1RA) 证明.
两种服用途径都没有引起显著的全身炎症或不良临床影响.

结论:

在RM中进行皮下GM-CSF的使用有效地扩大,激活和贩运系统性和粘膜性髓状细胞.
局部的GM-CSF对免疫细胞种群的影响最小.
这些发现为利用subQ GM-CSF作为辅助剂在临床环境中增强免疫反应提供了动力框架.

关键词:

转基因-CSFF 的时间.粘膜免疫力粘膜免疫力骨髓状细胞细胞是什么?rhesus macaques 是一种类型的.

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