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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function1. 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.

Original languageEnglish (US)
Pages (from-to)399-406
Number of pages8
Issue number8003
StatePublished - Mar 14 2024

All Science Journal Classification (ASJC) codes

  • General


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