Jiao Haifeng, Li Xiaopeng, Li Ying, Guo Ziyi, Yang Yuzhuo, Luo Yiqun, Hu Xiaoyu, Yu Li
State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China.
Institute for Immunology, Tsinghua University-Peking University Joint Centre for Life Sciences, School of Medicine, Tsinghua University, Beijing, China.
Cell Discov. 2024 Dec 9;10(1):121. doi: 10.1038/s41421-024-00749-x.
In dynamic systems like the circulatory system, establishing localized cytokine gradients is challenging. Upon lipopolysaccharide (LPS) stimulation, we observed that monocytes release numerous migrasomes enriched with inflammatory cytokines, such as TNF-α and IL-6. These cytokines are transported into migrasomes via secretory carriers, leading to their immediate exocytosis or eventual release from detached migrasomes. We successfully isolated TNF-α and IL-6-enriched, monocyte-derived migrasomes from the blood of LPS-treated mice. Total secretion analysis revealed a substantial amount of TNF-α and IL-6 released in a migrasome-packaged form. Thus, detached, monocyte-derived migrasomes represent a type of extracellular vesicle highly enriched with cytokines. Physiologically, these cytokine-laden migrasomes rapidly accumulate at local sites of inflammation, effectively creating a concentrated source of cytokines. Our research uncovers novel mechanisms for cytokine release and delivery, providing new insights into immune response modulation.
在诸如循环系统这样的动态系统中，建立局部细胞因子梯度具有挑战性。在脂多糖（LPS）刺激下，我们观察到单核细胞释放大量富含炎性细胞因子（如TNF-α和IL-6）的迁移小体。这些细胞因子通过分泌载体转运到迁移小体中，导致它们立即胞吐或最终从脱离的迁移小体中释放。我们成功地从LPS处理的小鼠血液中分离出富含TNF-α和IL-6的单核细胞来源的迁移小体。总分泌分析显示，大量的TNF-α和IL-6以迁移小体包装的形式释放。因此，脱离的、单核细胞来源的迁移小体代表了一种高度富含细胞因子的细胞外囊泡类型。在生理上，这些载有细胞因子的迁移小体迅速在炎症局部部位积累，有效地形成了细胞因子的浓缩来源。我们的研究揭示了细胞因子释放和递送的新机制，为免疫反应调节提供了新的见解。
