title: Chemical synthesis of a two-photon-activatable chemokine and photon-guided lymphocyte migration in vivo.
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.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Tang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China.
authors.forename: Ji-Shen
authors.initials: JS
authors.lastname: Zheng
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China.
authors.forename: Ruozhu
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Wang
authors.affiliation: Laboratory for Stem Cells and Epigenetics, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Shao
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Hao-Nan
authors.initials: HN
authors.lastname: Chang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Cheng
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000138:chemical synthesis*; D002633:Chemotaxis; D006801:Humans; D051379:Mice; D055668:Photochemical Processes; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5