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

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Cite this article as: eLife 2015;4:e10024 doi: 10.7554/eLife.10024

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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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Author details

Lian He

Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States

Competing interests
The authors declare that no competing interests exist.
Yuanwei Zhang

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical school, Worcester, United States

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The authors declare that no competing interests exist.
Guolin Ma

Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States

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The authors declare that no competing interests exist.
Peng Tan

Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States

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The authors declare that no competing interests exist.
Zhanjun Li

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States

Competing interests
The authors declare that no competing interests exist.
Shengbing Zhang

Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States

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The authors declare that no competing interests exist.
Xiang Wu

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States

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The authors declare that no competing interests exist.
Ji Jing

Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States

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The authors declare that no competing interests exist.
Shaohai Fang

Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States

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The authors declare that no competing interests exist.
Lijuan Zhou

Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Youjun Wang

Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China

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The authors declare that no competing interests exist.
Yun Huang

Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States

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The authors declare that no competing interests exist.
Patrick Hogan

Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, United States

Competing interests
The authors declare that no competing interests exist.
Gang Han

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States

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The authors declare that no competing interests exist.
Yubin Zhou

Center for Translational Cancer Research, Texas A&M University Health Science Center, Houston, United States

For correspondence
yzhou@ibt.tamhsc.edu

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The authors declare that no competing interests exist.

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).

Reviewing Editor

Richard Aldrich, The University of Texas at Austin, United States

Publication history

Received: July 11, 2015
Accepted: November 6, 2015
Accepted Manuscript published: December 8, 2015 (version 1)
Version of Record published: December 29, 2015 (version 2)
Version of Record updated: June 13, 2017 (version 3)

Copyright

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.