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

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 dev...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2015-05, Vol.6 (1), p.7220-7220, Article 7220
Main Authors: Chen, Xin, Tang, Shan, Zheng, Ji-Shen, Zhao, Ruozhu, Wang, Zhi-Peng, Shao, Wen, Chang, Hao-Nan, Cheng, Jing-Yuan, Zhao, Hui, Liu, Lei, Qi, Hai
Format: Article
Language:English
Subjects:
13/31
14/19
14/69
631/250/1619
631/250/98
631/80/84
631/92/95
Animals
Cells, Cultured
Chemokine CCL5 - chemical synthesis
Chemotaxis
Humanities and Social Sciences
Humans
Mice
multidisciplinary
Photochemical Processes
Science
Science (multidisciplinary)
T-Lymphocytes - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 . The precise spatiotemporal control of chemokine exposure would be an advantageous tool for immune cell research. Here, Chen et al. develop a two-photon-activatable chemokine CCL5 and use it to direct lymphocyte migration in vivo and to show that PI3-kinase is not required to sense a gradient in vitro .
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms8220