Near-infrared photoactivatable control of Ca2+ signaling and optogenetic immunomodulation

  1. Lian He
  2. Yuanwei Zhang
  3. Guolin Ma
  4. Peng Tan
  5. Zhanjun Li
  6. Shengbing Zhang
  7. Xiang Wu
  8. Ji Jing
  9. Shaohai Fang
  10. Lijuan Zhou
  11. Youjun Wang
  12. Yun Huang
  13. Patrick Hogan
  14. Gang Han
  15. Yubin Zhou  Is a corresponding author
  1. Texas A&M University Health Science Center, United States
  2. University of Massachusetts Medical school, United States
  3. University of Massachusetts Medical School, United States
  4. Beijing Normal University, China
  5. 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.

Article and author information

Author details

  1. 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.
  2. Yuanwei Zhang

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical school, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Guolin Ma

    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.
  4. Peng Tan

    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.
  5. 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.
  6. Shengbing Zhang

    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.
  7. Xiang Wu

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Ji Jing

    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.
  9. Shaohai Fang

    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.
  10. 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.
  11. Youjun Wang

    Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Yun Huang

    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.
  13. 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.
  14. Gang Han

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Yubin Zhou

    Center for Translational Cancer Research, Texas A&M University Health Science Center, Houston, United States
    For correspondence
    yzhou@ibt.tamhsc.edu
    Competing interests
    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

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

Publication history

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

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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  1. Lian He
  2. Yuanwei Zhang
  3. Guolin Ma
  4. Peng Tan
  5. Zhanjun Li
  6. Shengbing Zhang
  7. Xiang Wu
  8. Ji Jing
  9. Shaohai Fang
  10. Lijuan Zhou
  11. Youjun Wang
  12. Yun Huang
  13. Patrick Hogan
  14. Gang Han
  15. Yubin Zhou
(2015)
Near-infrared photoactivatable control of Ca2+ signaling and optogenetic immunomodulation
eLife 4:e10024.
https://doi.org/10.7554/eLife.10024

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