Volume 7, Issue 2, December 2019, Page: 22-29
Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation
Dong Woo Ko, School of Computer Science and Information Engineering, The Catholic University of Korea, Bucheon, South Korea
Jeesang Yoon, Department of Biotechnology, Yonsei University, Seoul, Korea
Jung Jin Yang, School of Computer Science and Information Engineering, The Catholic University of Korea, Bucheon, South Korea
Received: Nov. 21, 2019;       Accepted: Dec. 9, 2019;       Published: Jan. 4, 2020
DOI: 10.11648/j.cbb.20190702.12      View  378      Downloads  99
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.
Regulatory T Cells, Integrative Bioinformatics, DEG, Functional Gene Network, Slc39a8, Immunosuppression
To cite this article
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, Computational Biology and Bioinformatics. Vol. 7, No. 2, 2019, pp. 22-29. doi: 10.11648/j.cbb.20190702.12
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This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
E. G. Schmitt, C. B. Williams, Generation and function of induced regulatory T cells, Frontiers in immunology, 4 pp. 152, 2013.
A. Liston, D. H. Gray, Homeostatic control of regulatory T cell diversity, Nature Reviews Immunology, 14 pp. 154-165, 2014.
P. Trzonkowski, M. Bieniaszewska, J. Juścińska, A. Dobyszuk, A. Krzystyniak, N. Marek, J. Myśliwska, A. Hellmann, First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+ CD25+ CD127− T regulatory cells, Clinical immunology, 133 pp. 22-26, 2009.
A. H. Sharpe, K. E. Pauken, The diverse functions of the PD1 inhibitory pathway, Nature Reviews Immunology, 18 pp. 153, 2018.
X. Wang, Z. Bao, X. Zhang, F. Li, T. Lai, C. Cao, Z. Chen, W. Li, H. Shen, S. Ying, Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis, Oncotarget, 8 pp. 59901-59914, 2017.
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.
D. A. Knee, B. Hewes, J. L. Brogdon, Rationale for anti-GITR cancer immunotherapy, European journal of cancer, 67 pp. 1-10, 2016.
N. Bray, H. Pimentel, P. Melsted et al. Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol 34, pp. 525–527, 2016.
P. Compeau, P. Pevzner, G. Tesler, How to apply de Bruijn graphs to genome assembly. Nat Biotechnol 29, pp. 987–991, 2011.
V. A. Schneider, T. Graves-Lindsay et al. Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly. August 2016.
L. V. Maaten, G. Hinton, Visualizing Data using t-SNE. Journal of Machine Learning Research 9: pp. 2579-2605, 2008.
J. A. Lee and M. Verleysen. Nonlinear dimensionality reduction. Springer, New York, NY, USA, 2007.
S. Hojyo, T. Fukada, Roles of zinc signaling in the immune system, Journal of immunology research, 2016.
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.
E. Batlle, J. Massagué. Transforming growth factor-β signaling in immunity and cancer. Immunity. 50. pp. 924-940, 2019.
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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