Manipulating leukocyte interactions in vivo through optogenetic chemokine release.
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Sarris, M., Olekhnovitch, R., & Bousso, P. (2016). Manipulating leukocyte interactions in vivo through optogenetic chemokine release.. Blood, 127 (23), e35-e41. https://doi.org/10.1182/blood-2015-11-684852
Light-mediated release of signaling ligands, such as chemoattractants, growth factors, and cytokines is an attractive strategy for investigation and therapeutic targeting of leukocyte communication and immune responses. We introduce a versatile optogenetic method to control ligand secretion, combining UV-conditioned endoplasmic reticulum-to-Golgi trafficking and a furin-processing step. As proof of principle, we achieved light-triggered chemokine secretion and demonstrated that a brief pulse of chemokine release can mediate a rapid flux of leukocyte contacts with target cells in vitro and in vivo. This approach opens new possibilities for dynamic investigation of leukocyte communication in vivo and may confer the potential to control the local release of soluble mediators in the context of immune cell therapies.
Animals, Animals, Genetically Modified, Cell Communication, Chemokines, Chemotactic Factors, Chemotaxis, Leukocyte, Embryo, Nonmammalian, HEK293 Cells, Humans, Leukocytes, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Optogenetics, Signal Transduction, Zebrafish
This work was supported by Institut Pasteur, INSERM, the European Research Council (starting grant LymphocyteContacts) (P.B.), and the Medical Research Council (RG73189) (M.S.).
Royal Society (RG170240)
External DOI: https://doi.org/10.1182/blood-2015-11-684852
This record's URL: https://www.repository.cam.ac.uk/handle/1810/255720