Near-infrared photoactivatable control of Ca2+ signaling and optogenetic immunomodulation
- Texas A&M University Health Science Center, United States
- University of Massachusetts Medical school, United States
- University of Massachusetts Medical School, United States
- Beijing Normal University, China
- La Jolla Institute for Allergy and Immunology, United States
Abstract
The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed "Opto-CRAC") that selectively and remotely controls Ca2+ oscillations and Ca2+-responsive gene expression to regulate the function of non-excitable cells, including T lymphocytes, macrophages and dendritic cells. When coupled to upconversion nanoparticles, the optogenetic operation window is shifted from the visible range to NIR wavelengths to enable wireless photoactivation of Ca2+-dependent signaling and optogenetic modulation of immunoinflammatory responses. In a mouse model of melanoma by using ovalbumin as surrogate tumor antigen, Opto-CRAC has been shown to act as a genetically-encoded "photoactivatable adjuvant" to improve antigen-specific immune responses to specifically destruct tumor cells. Our study represents a solid step forward towards the goal of achieving remote control of Ca2+-modulated activities with tailored function.
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Ethics
Animal experimentation: Mice-related experiments were approved by Institutional Animal Care and Use Committees of Institute of Biosciences and Technology, Texas A&M University Health Science Center (#12044 and #2014-0228-IBT; Houston, TX, USA; Animal Welfare Assurance Number A3893-01) and University of Massachusetts Medical School (#A-2512-15, Worcester, MA, USA; Animal Welfare Assurance Number A3306-01).
Copyright
© 2015, He et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Near-infrared photoactivatable control of Ca2+ signaling and optogenetic immunomodulation
eLife 4:e10024.
https://doi.org/10.7554/eLife.10024
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