Chemical synthesis of a two-photon-activatable chemokine and photon-guided lymphocyte migration in vivo
Citations Over TimeTop 10% of 2015 papers
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.
Related Papers
- → HIV-1-Induced miR-146a Attenuates Monocyte Migration by Targeting CCL5 in Human Primary Macrophages(2018)20 cited
- → Production of Rantes/CCL5 in human gingival fibroblasts challenged with tumor necrosis factor α(2001)11 cited
- → The CC chemokine RANTES (CCL5) mediates liver fibrosis in mice and humans(2008)2 cited
- → Synergy between IL-8 and GM–CSF in reproductive tract epithelial cell secretions promotes enhanced neutrophil chemotaxis(2004)39 cited
- → Changes in the Profiles of Chemokines Secreted by Endothelial Cells and Monocytes under Different Coculturing Conditions(2011)5 cited