Chemical synthesis of a two-photon-activatable chemokine and photon-guided lymphocyte migration in vivo

Xin Chen, Shan Tang, Ji-Shen Zheng, Ruozhu Zhao, Zhi-Peng Wang, Wen Shao, Hao-Nan Chang, Jing-Yuan Cheng, Hui Zhao, Lei Liu () and Hai Qi ()
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Xin Chen: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University
Shan Tang: Tsinghua-Peking Center for Life Sciences, Tsinghua University
Ji-Shen Zheng: High Magnetic Field Laboratory, Chinese Academy of Sciences
Ruozhu Zhao: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University
Zhi-Peng Wang: Tsinghua-Peking Center for Life Sciences, Tsinghua University
Wen Shao: Laboratory for Stem Cells and Epigenetics, School of Medicine, Tsinghua University
Hao-Nan Chang: Tsinghua-Peking Center for Life Sciences, Tsinghua University
Jing-Yuan Cheng: Tsinghua-Peking Center for Life Sciences, Tsinghua University
Hui Zhao: School of Life Sciences, Tsinghua University
Lei Liu: Tsinghua-Peking Center for Life Sciences, Tsinghua University
Hai Qi: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract Chemokine-guided lymphocyte positioning in tissues is crucial for normal operation of the immune system. Direct, real-time manipulation and measurement of single-cell responses to chemokines is highly desired for investigating the cell biology of lymphocyte migration in vivo. Here we report the development of the first two-photon-activatable chemokine CCL5 through efficient one-pot total chemical synthesis in milligram scale. By spatiotemporally controlled photoactivation, we show at the single-cell level that T cells perceive the directional cue without relying on PI3K activities, which are nonetheless required for persistent migration over an extended period of time. By intravital imaging, we demonstrate artificial T-cell positioning in cutaneous tissues and lymph nodes. This work establishes a general strategy to develop high-quality photo-activatable protein agents through tailor-designed caging of multiple residues and highlights the potential of photo-activatable chemokines for understanding and potential therapeutic manipulation of cell positioning and position-controlled cell behaviours in vivo.

Date: 2015
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DOI: 10.1038/ncomms8220

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