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Universal recording of immune cell interactions in vivo

ABSTRACT: Universal recording of immune cell interactions in vivo

PROVIDER: PRJNA1063627 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27501652_1.fastq.gz	Fastqsanger.gz
	SRR27501652_2.fastq.gz	Fastqsanger.gz
	SRR27501653_1.fastq.gz	Fastqsanger.gz
	SRR27501653_2.fastq.gz	Fastqsanger.gz
	SRR27501654_1.fastq.gz	Fastqsanger.gz

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Universal recording of immune cell interactions in vivo

Project description: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 (Labeling Immune Partnerships by SorTagging Intercellular Contacts), an approach that uses enzymatic transfer of a labeled 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+ helper T 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 (Treg) cells, and identify germinal center (GC)-resident T follicular helper (Tfh) cells based on their ability to interact cognately with GC B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalog of the immune populations that physically interact with intestinal epithelial cells (IECs) at steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cells in multiple organs upon systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell–cell interactions across multiple biological systems.

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Universal recording of immune cell interactions in vivo.

Project description: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.

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