Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-activated Human CD4+ T Cells Exhibiting Varied Levels of CHRNA7 and CHRFAM7A Expression

Masato Mashimo
ORCID logo ,
Takeshi Fujii
,
Shiro Ono
,
Yasuhiro Moriwaki
ORCID logo ,
Hidemi Misawa
,
Tetsushi Azami
,
Tadashi Kasahara
,
Koichiro Kawashima
*
Version 1 : Received: 14 June 2023 / Approved: 15 June 2023 / Online: 15 June 2023 (07:33:48 CEST)

A peer-reviewed article of this Preprint also exists.

Mashimo, M.; Fujii, T.; Ono, S.; Moriwaki, Y.; Misawa, H.; Azami, T.; Kasahara, T.; Kawashima, K. GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4+ T Cells Exhibiting Varied Levels of CHRNA7 and CHRFAM7A Expression. Int. J. Mol. Sci. 2023, 24, 12257. Mashimo, M.; Fujii, T.; Ono, S.; Moriwaki, Y.; Misawa, H.; Azami, T.; Kasahara, T.; Kawashima, K. GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4+ T Cells Exhibiting Varied Levels of CHRNA7 and CHRFAM7A Expression. Int. J. Mol. Sci. 2023, 24, 12257.

Abstract

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+ 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 CD+ 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+ 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.

Keywords

acetylcholine; adoptive immunotherapy; α7; dupα7; GTS-21; nAChR; Treg

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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