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

Author

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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)

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.

Suggested Citation

  • Xin Chen & Shan Tang & Ji-Shen Zheng & Ruozhu Zhao & Zhi-Peng Wang & Wen Shao & Hao-Nan Chang & Jing-Yuan Cheng & Hui Zhao & Lei Liu & Hai Qi, 2015. "Chemical synthesis of a two-photon-activatable chemokine and photon-guided lymphocyte migration in vivo," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8220
    DOI: 10.1038/ncomms8220
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