Universal recording of immune cell interactions in vivo

• 成果类型: Article
• 署名作者: Nakandakari-Higa, Sandra; Walker, Sarah; Canesso, Maria C. C.; van der Heide, Verena; Chudnovskiy, Aleksey; Kim, Dong-Yoon; Jacobsen, Johanne T.; Parsa, Roham; Bilanovic, Jana; Parigi, S. Martina; Fiedorczuk, Karol; Fuchs, Elaine; Bilate, Angelina M.; Pasqual, Giulia; Mucida, Daniel; Kamphorst, Alice O.; Pritykin, Yuri; Victora, Gabriel D.
• 署名单位: Rockefeller University; Princeton University; Princeton University; Rockefeller University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Rockefeller University; Rockefeller University; Rockefeller University; Howard Hughes Medical Institute; University of Padua; Princeton University; University of Oslo; National Hospital Norway
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4537
• DOI: 10.1038/s41586-024-07134-4
• 发表日期: 2024-03-14
• 页码: 399-406
• 关键词: lymphocytic choriomeningitis virus; dendritic cells; transgenic mice; expression; selection; adhesion; MODEL; differentiation; generation; adaptation

摘要

Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function(1). To study these 'kiss-and-run' interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts)(2), 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.