用于监测CCR2配体在培养和体内时空动态的遗传编码生物传感器，这一成果由西湖大学Kiryl D. Piatkevich研究组经过不懈努力而取得。该研究于2025年7月15日发表于国际一流学术期刊《自然—方法学》杂志上。

研究团队报道了一种基因编码的绿色荧光趋化因子传感器的工程和特性，命名为CRAFi-CCR2，它利用CCR2受体作为传感片段。在星形胶质细胞中，源自人CCR2B受体的hCRAFi-CCR2对mCCL2的荧光反应增加了~300%，具有纳摩尔亲和力（2.5nM）。hCRAFi-CCR2的激活不影响下游信号通路，如钙动员和受体内化。使用该传感器，该课题组执行了17-20 h实时成像，观察细胞培养和小鼠炎症条件下内源性mCCL2的释放。在单主题脑中，该研究团队观察到CCL2信号反应的空间异质性，其范围约为20-50 μm，强调了免疫系统时空信号的复杂性。

据介绍，趋化因子调节免疫细胞在发育、稳态和炎症中的迁移，但由于现有检测方法的限制，趋化因子在体内释放的精确时空模式仍然是未知的。

附：英文原文

Title: Genetically encoded biosensor for monitoring spatiotemporal dynamics of CCR2 ligands in culture and in vivo

Author: Xiao, Xian, Wang, Chenyu, Guo, Xun, Xi, Fengxue, Qian, Qiuling, Liang, Guoteng, Chen, Ming, Sun, Xiaoting, Szabo, Balint, Jing, Miao, Piatkevich, Kiryl D.

Issue&Volume: 2025-07-15

Abstract: Chemokines regulate immune cell migration in development, homeostasis and inflammation, but the precise spatiotemporal pattern of chemokine release in vivo remains elusive due to the constraints of existing detection methodologies. Here, we report the engineering and characterization of a genetically encoded green fluorescent chemokine sensor, named CRAFi-CCR2, which utilizes the CCR2 receptor as a sensing moiety. In astrocytes, hCRAFi-CCR2, derived from the human CCR2B receptor, exhibited ~300% increase in fluorescence in response to mCCL2, with nanomolar affinity (2.5nM). Activation of hCRAFi-CCR2 did not affect downstream signaling pathways, such as calcium mobilization and receptor internalization. Using this sensor, we performed 17–20h of real-time imaging to observe endogenous mCCL2 release under inflammatory conditions, both in cell culture and in mice. In mouse brain, we observed spatial heterogeneity of CCL2 signal response on a scale of about 20–50μm, highlighting the complexity of the immune system’s spatiotemporal signaling.

DOI: 10.1038/s41592-025-02742-y

Source: https://www.nature.com/articles/s41592-025-02742-y