Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation
| Autor: | Dong Woo Ko, Jeesang Yoon, Jung Jin Yang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Naive T cell
Regulatory T cell medicine.medical_treatment T cell General Engineering FOXP3 hemic and immune systems chemical and pharmacologic phenomena Biology Cell biology MRNA Sequencing Cytokine medicine.anatomical_structure medicine General Earth and Planetary Sciences IL-2 receptor Transcription factor General Environmental Science |
| Zdroj: | Computational Biology and Bioinformatics. 7:22 |
| ISSN: | 2330-8265 |
| DOI: | 10.11648/j.cbb.20190702.12 |
| Popis: | 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 naive 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. |
| Databáze: | OpenAIRE |
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