血中のT細胞が血圧や炎症に影響を与える物質を分泌する(T cells in blood secrete a substance that affects blood pressure and inflammation)

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2023-03-30 カロリンスカ研究所(KI)

研究者たちは、ヒトのT細胞がアセチルコリンを生産することを発見しました。
これは、血圧と炎症を調節するのに役立ちます。この研究は、PNASに掲載され、重症患者の免疫細胞と死亡リスクの可能性のある関連性も示しています。
今後、研究者たちは、ChAT+ T細胞の存在を患者グループや様々な臓器で調べ、代謝や炎症プロセスに与える影響について研究する予定です。

<関連情報>

ヒトChAT+ T細胞によるコリン作動性血管内皮機能制御機構 Cholinergic regulation of vascular endothelial function by human ChAT+ T cells

Laura Tarnawski,Vladimir S. Shavva,Eric J. Kort,Zhengbing Zhuge,Ingrid Nilsson,Alessandro L. Gallina,David Martínez-Enguita ,Benjamin Heller Sahlgren,Matthew Weiland,April S. Caravaca,Staffan Schmidt,Ping Chen,Katarina Abbas,Fu-Hua Wang,Osman Ahmed,Michael Eberhardson,Anna Färnert,Eddie Weitzberg,Mika Gustafsson,Jan Kehr,Stephen G. Malin,Henrik Hult,Mattias Carlström ,Stefan Jovinge,Peder S. Olofsson
Proceedings of the National Academy of Sciences  Published:March 29, 2023
DOI:https://doi.org/10.1073/pnas.2212476120

 

Significance

ACh-releasing choline acetyltransferase (ChAT)+ T cells promote vasodilation and regulate blood pressure in mice, but human ChAT+ T cells and the molecular mechanisms by which ChAT-expression is regulated remain undefined. In this study, we identify primary ChAT+ T cells in patients and regulatory mechanisms for ChAT expression in T cells. Interestingly, cholinergic signals from T cells regulated vascular endothelial function in vitro.

Abstract

Endothelial dysfunction and impaired vasodilation are linked with adverse cardiovascular events. T lymphocytes expressing choline acetyltransferase (ChAT), the enzyme catalyzing biosynthesis of the vasorelaxant acetylcholine (ACh), regulate vasodilation and are integral to the cholinergic antiinflammatory pathway in an inflammatory reflex in mice. Here, we found that human T cell ChAT mRNA expression was induced by T cell activation involving the PI3K signaling cascade. Mechanistically, we identified that ChAT mRNA expression was induced following the attenuation of RE-1 Silencing Transcription factor REST-mediated methylation of the ChAT promoter, and that ChAT mRNA expression levels were up-regulated by GATA3 in human T cells. In functional experiments, T cell-derived ACh increased endothelial nitric oxide-synthase activity, promoted vasorelaxation, and reduced vascular endothelial activation and promoted barrier integrity by a cholinergic mechanism. Further, we observed that survival in a cohort of patients with severe circulatory failure correlated with their relative frequency of ChAT +CD4+ T cells in blood. These findings on ChAT+ human T cells provide a mechanism for cholinergic immune regulation of vascular endothelial function in human inflammation.

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