2. Academic Validation
  3. Spatiotemporal dynamics of CXCL10 encode contextual immune information revealed by the genetically encoded fluorescent sensor

Spatiotemporal dynamics of CXCL10 encode contextual immune information revealed by the genetically encoded fluorescent sensor

  • Immunity. 2025 Sep 9;58(9):2320-2335.e9. doi: 10.1016/j.immuni.2025.07.005.
Fengxue Xi 1,  Chenyu Wang 1,  Yuanxia Wang 1,  Pengwei Luan 2,  Yue Chen 3,  Luqiao Tan 3,  Nianhan Shang 3,  Xinwei Gao 3,  Daoming Chen 4,  Qingchun Guo 5,  Ting Chen 4,  Miao Jing 6
Affiliations

Affiliations

  • 1 Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing 102206, China.
  • 2 Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing 102206, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • 3 Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing 102206, China.
  • 4 National Institute of Biological Sciences, Beijing 102206, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 100084, China.
  • 5 Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing 102206, China; School of Biomedical Engineering, Capital Medical University, Beijing 100069, China.
  • 6 Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing 102206, China. Electronic address: jingmiao@cibr.ac.cn.
PMID: 40818452 DOI: 10.1016/j.immuni.2025.07.005
Abstract

Chemokines are key extracellular signals that guide cell migration and immune homeostasis, yet how they convey information through their dynamic patterns remains elusive. We engineered a genetically encoded fluorescent sensor, a G protein-coupled receptor (GPCR) activation-based sensor (GRAB)-LoX3-1.0, for the chemokine CXCL10 by inserting a circularly permutated fluorescent protein into the Chemokine Receptor CXCR3. The sensor exhibited a high signal-to-noise ratio, nanomolar affinity, rapid temporal resolution, and submicrometer spatial resolution that collectively enabled precise mapping of chemokine dynamics. Using LoX3-1.0, we monitored the temporal patterns of chemokines shaped by distinct inflammatory states and quantitatively revealed the multidimensional features of chemokine signaling and its potential organizational principles. In vivo, we directly visualized micrometer-scale CXCL10 gradients and their evolution surrounding blood vessels during brain neuroinflammation and also tracked the injury-induced CXCL10 dynamics in the peripheral skin of mice. Collectively, LoX3-1.0 enabled direct visualization of CXCL10 spatiotemporal organization, which functions as context-specific signaling codes conveying environmental information across inflammatory states.

Keywords

CXCL10; CXCR3; chemokine; fluorescent sensor; in vivo imaging; neuroinflammation; spatiotemporal dynamics.

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