GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of <i>CHRNA7</i> and <i>CHRFAM7A</i> Expression
Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4...
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/12257 |
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| author | Masato Mashimo Takeshi Fujii Shiro Ono Yasuhiro Moriwaki Hidemi Misawa Tetsushi Azami Tadashi Kasahara Koichiro Kawashima |
| author_facet | Masato Mashimo Takeshi Fujii Shiro Ono Yasuhiro Moriwaki Hidemi Misawa Tetsushi Azami Tadashi Kasahara Koichiro Kawashima |
| author_sort | Masato Mashimo |
| collection | DOAJ |
| description | Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4<sup>+</sup> T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD4<sup>+</sup> T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4<sup>+</sup> T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit. |
| first_indexed | 2024-03-11T00:25:16Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:25:16Z |
| publishDate | 2023-07-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-417b3d0c56cd48df95416d82120283392023-11-18T23:02:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151225710.3390/ijms241512257GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of <i>CHRNA7</i> and <i>CHRFAM7A</i> ExpressionMasato Mashimo0Takeshi Fujii1Shiro Ono2Yasuhiro Moriwaki3Hidemi Misawa4Tetsushi Azami5Tadashi Kasahara6Koichiro Kawashima7Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe 610-0395, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, Kyotanabe 610-0395, JapanLaboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi 584-8540, JapanDepartment of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, JapanDepartment of Pharmacology, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, JapanDivision of Gastroenterology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama 227-8502, JapanDivision of Inflammation Research, Jichi Medical University, Shimotsukeshi 324-0498, JapanDepartment of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo 108-8641, JapanImmune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4<sup>+</sup> T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD4<sup>+</sup> T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4<sup>+</sup> T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.https://www.mdpi.com/1422-0067/24/15/12257acetylcholineadoptive immunotherapyα7dupα7GTS-21nAChR |
| spellingShingle | Masato Mashimo Takeshi Fujii Shiro Ono Yasuhiro Moriwaki Hidemi Misawa Tetsushi Azami Tadashi Kasahara Koichiro Kawashima GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of <i>CHRNA7</i> and <i>CHRFAM7A</i> Expression International Journal of Molecular Sciences acetylcholine adoptive immunotherapy α7 dupα7 GTS-21 nAChR |
| title | GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of <i>CHRNA7</i> and <i>CHRFAM7A</i> Expression |
| title_full | GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of <i>CHRNA7</i> and <i>CHRFAM7A</i> Expression |
| title_fullStr | GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of <i>CHRNA7</i> and <i>CHRFAM7A</i> Expression |
| title_full_unstemmed | GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of <i>CHRNA7</i> and <i>CHRFAM7A</i> Expression |
| title_short | GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of <i>CHRNA7</i> and <i>CHRFAM7A</i> Expression |
| title_sort | gts 21 enhances regulatory t cell development from t cell receptor activated human cd4 sup sup t cells exhibiting varied levels of i chrna7 i and i chrfam7a i expression |
| topic | acetylcholine adoptive immunotherapy α7 dupα7 GTS-21 nAChR |
| url | https://www.mdpi.com/1422-0067/24/15/12257 |
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