マイクロスコープが細胞時間の凍結した瞬間を明らかにする。この新しい方法は、細胞が働く様子を記録する。(Microscopes reveal a frozen moment in cellular time. This new method records cells as they work.)

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2024-04-08 プリンストン大学

プリンストン大学とロックフェラー大学の研究者は、生きている生物の中での細胞間の相互作用を記録し、体の機能を理解するための新しい方法を開発しました。これにより、細胞が病気と戦ったり組織を形成したりする仕組みをより詳しく理解できるようになりました。この研究は、Nature誌に掲載され、コンピュータサイエンス助教授のユーリ・プリティキンが共同執筆者として参加しています。

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生体内での免疫細胞相互作用の普遍的記録 Universal recording of immune cell interactions in vivo

Sandra Nakandakari-Higa,Sarah Walker,Maria C. C. Canesso,Verena van der Heide,Aleksey Chudnovskiy,Dong-Yoon Kim,Johanne T. Jacobsen,Roham Parsa,Jana Bilanovic,S. Martina Parigi,Karol Fiedorczuk,Elaine Fuchs,Angelina M. Bilate,Giulia Pasqual,Daniel Mucida,Alice O. Kamphorst,Yuri Pritykin & Gabriel D. Victora
Nature  Published:06 March 2024
DOI:https://doi.org/10.1038/s41586-024-07134-4

extended data figure 1

Abstract

Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function. To study these ‘kiss-and-run’ interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts), an approach that uses enzymatic transfer of a labelled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4+ T helper cells and antigen-presenting cells, however. Here we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8+ T cells by dendritic cells, reveal the steady-state cellular partners of regulatory T cells and identify germinal centre-resident T follicular helper cells on the basis of their ability to interact cognately with germinal centre B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalogue of the immune populations that physically interact with intestinal epithelial cells at the steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus-specific CD8+ T cells in multiple organs following systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell–cell interactions across multiple biological systems.

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