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Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation

Received: 21 November 2019     Accepted: 9 December 2019     Published: 4 January 2020
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Abstract

Regulatory T cell (Treg cell) is a subset of T cell expressing Foxp3 transcription factor and critical for maintaining the immunological homeostasis in autoimmune micro-environment. However, the absence of the surface marker specific to Treg cell is the major barrier for the development of therapeutic reagent targeting Treg cells. To identify a novel gene specific to Treg cells mRNA sequencing data about naïve T cell, activated T cells (Th0), TH1 and Treg cells were processed by integrative bioinformatic methods and 350 Differentially Expressed Genes (DEGs) specific to Treg cells were selected. Using the bioinformatic program to score the intracellular location and functional gene network analysis to measure the functional relationship to Foxp3 Slc39a8 gene encoding zinc transport on the surface of Treg cells was chosen as a final candidate. The protein expression of the Slc39a8 gene was highly specific to Treg cells among various T cell subsets, and its expression was induced by TGF-β. In a dose-dependent manner, which is the key immuno-suppressive cytokine. The immuno-suppressive capacity of CD4+/Slc39a8+ T cells toward the activated T cells was substantially higher than that of CD4+/CD25+ T cells in a contact-independent way. Taken these results together, Slc39a8 was identified as a novel Treg cell-specific marker encoding a zinc transporter on the surface, which is functionally important for Treg cells. Therefore, Slc39a8 will serve as a new target molecule to develop the therapeutics for the treatment of various autoimmune diseases and solid cancers.

Published in Computational Biology and Bioinformatics (Volume 7, Issue 2)
DOI 10.11648/j.cbb.20190702.12
Page(s) 22-29
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2020. Published by Science Publishing Group

Keywords

Regulatory T Cells, Integrative Bioinformatics, DEG, Functional Gene Network, Slc39a8, Immunosuppression

References
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[6] L. T. Krausz, R. Bianchini, S. Ronchetti, K. Fettucciari, G. Nocentini, C. Riccardi, GITR-GITRL system, a novel player in shock and inflammation, The Scientific World Journal, 7 pp. 533-566, 2007.
[7] D. A. Knee, B. Hewes, J. L. Brogdon, Rationale for anti-GITR cancer immunotherapy, European journal of cancer, 67 pp. 1-10, 2016.
[8] N. Bray, H. Pimentel, P. Melsted et al. Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol 34, pp. 525–527, 2016.
[9] P. Compeau, P. Pevzner, G. Tesler, How to apply de Bruijn graphs to genome assembly. Nat Biotechnol 29, pp. 987–991, 2011.
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[12] J. A. Lee and M. Verleysen. Nonlinear dimensionality reduction. Springer, New York, NY, USA, 2007.
[13] S. Hojyo, T. Fukada, Roles of zinc signaling in the immune system, Journal of immunology research, 2016.
[14] X. Meng, J. Yang, M. Dong, K. Zhang, E. Tu, Q. Gao, W. Chen, C. Zhang, Y. Zhang, Regulatory T cells in cardiovascular diseases, Nature Reviews Cardiology, 13 pp. 167, 2016.
[15] E. Batlle, J. Massagué. Transforming growth factor-β signaling in immunity and cancer. Immunity. 50. pp. 924-940, 2019.
[16] M. Yu, W. W. Lee, D. Tomar et al. Regulation of T cell receptor signaling by activation-induced zinc influx. J Exp Med. 208. pp. 775-785, 2011.
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  • APA Style

    Dong Woo Ko, Jeesang Yoon, Jung Jin Yang. (2020). Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation. Computational Biology and Bioinformatics, 7(2), 22-29. https://doi.org/10.11648/j.cbb.20190702.12

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    ACS Style

    Dong Woo Ko; Jeesang Yoon; Jung Jin Yang. Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation. Comput. Biol. Bioinform. 2020, 7(2), 22-29. doi: 10.11648/j.cbb.20190702.12

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    AMA Style

    Dong Woo Ko, Jeesang Yoon, Jung Jin Yang. Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation. Comput Biol Bioinform. 2020;7(2):22-29. doi: 10.11648/j.cbb.20190702.12

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  • @article{10.11648/j.cbb.20190702.12,
      author = {Dong Woo Ko and Jeesang Yoon and Jung Jin Yang},
      title = {Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation},
      journal = {Computational Biology and Bioinformatics},
      volume = {7},
      number = {2},
      pages = {22-29},
      doi = {10.11648/j.cbb.20190702.12},
      url = {https://doi.org/10.11648/j.cbb.20190702.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbb.20190702.12},
      abstract = {Regulatory T cell (Treg cell) is a subset of T cell expressing Foxp3 transcription factor and critical for maintaining the immunological homeostasis in autoimmune micro-environment. However, the absence of the surface marker specific to Treg cell is the major barrier for the development of therapeutic reagent targeting Treg cells. To identify a novel gene specific to Treg cells mRNA sequencing data about naïve T cell, activated T cells (Th0), TH1 and Treg cells were processed by integrative bioinformatic methods and 350 Differentially Expressed Genes (DEGs) specific to Treg cells were selected. Using the bioinformatic program to score the intracellular location and functional gene network analysis to measure the functional relationship to Foxp3 Slc39a8 gene encoding zinc transport on the surface of Treg cells was chosen as a final candidate. The protein expression of the Slc39a8 gene was highly specific to Treg cells among various T cell subsets, and its expression was induced by TGF-β. In a dose-dependent manner, which is the key immuno-suppressive cytokine. The immuno-suppressive capacity of CD4+/Slc39a8+ T cells toward the activated T cells was substantially higher than that of CD4+/CD25+ T cells in a contact-independent way. Taken these results together, Slc39a8 was identified as a novel Treg cell-specific marker encoding a zinc transporter on the surface, which is functionally important for Treg cells. Therefore, Slc39a8 will serve as a new target molecule to develop the therapeutics for the treatment of various autoimmune diseases and solid cancers.},
     year = {2020}
    }
    

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  • TY  - JOUR
    T1  - Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation
    AU  - Dong Woo Ko
    AU  - Jeesang Yoon
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    JO  - Computational Biology and Bioinformatics
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    UR  - https://doi.org/10.11648/j.cbb.20190702.12
    AB  - Regulatory T cell (Treg cell) is a subset of T cell expressing Foxp3 transcription factor and critical for maintaining the immunological homeostasis in autoimmune micro-environment. However, the absence of the surface marker specific to Treg cell is the major barrier for the development of therapeutic reagent targeting Treg cells. To identify a novel gene specific to Treg cells mRNA sequencing data about naïve T cell, activated T cells (Th0), TH1 and Treg cells were processed by integrative bioinformatic methods and 350 Differentially Expressed Genes (DEGs) specific to Treg cells were selected. Using the bioinformatic program to score the intracellular location and functional gene network analysis to measure the functional relationship to Foxp3 Slc39a8 gene encoding zinc transport on the surface of Treg cells was chosen as a final candidate. The protein expression of the Slc39a8 gene was highly specific to Treg cells among various T cell subsets, and its expression was induced by TGF-β. In a dose-dependent manner, which is the key immuno-suppressive cytokine. The immuno-suppressive capacity of CD4+/Slc39a8+ T cells toward the activated T cells was substantially higher than that of CD4+/CD25+ T cells in a contact-independent way. Taken these results together, Slc39a8 was identified as a novel Treg cell-specific marker encoding a zinc transporter on the surface, which is functionally important for Treg cells. Therefore, Slc39a8 will serve as a new target molecule to develop the therapeutics for the treatment of various autoimmune diseases and solid cancers.
    VL  - 7
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Author Information
  • School of Computer Science and Information Engineering, The Catholic University of Korea, Bucheon, South Korea

  • Department of Biotechnology, Yonsei University, Seoul, Korea

  • School of Computer Science and Information Engineering, The Catholic University of Korea, Bucheon, South Korea

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