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Dictionary of immune responses to cytokines at single-cell resolution

2023· article· en· 342 citations· W4389390583 on OpenAlex· 10.1038/s41586-023-06816-9

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Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

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Opus teacher head0.013
GPT teacher head0.244
Teacher spread
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Abstract

, yet we lack a global view of the cellular responses of each immune cell type to each cytokine. To address this gap, we created the Immune Dictionary, a compendium of single-cell transcriptomic profiles of more than 17 immune cell types in response to each of 86 cytokines (>1,400 cytokine-cell type combinations) in mouse lymph nodes in vivo. A cytokine-centric view of the dictionary revealed that most cytokines induce highly cell-type-specific responses. For example, the inflammatory cytokine interleukin-1β induces distinct gene programmes in almost every cell type. A cell-type-centric view of the dictionary identified more than 66 cytokine-driven cellular polarization states across immune cell types, including previously uncharacterized states such as an interleukin-18-induced polyfunctional natural killer cell state. Based on this dictionary, we developed companion software, Immune Response Enrichment Analysis, for assessing cytokine activities and immune cell polarization from gene expression data, and applied it to reveal cytokine networks in tumours following immune checkpoint blockade therapy. Our dictionary generates new hypotheses for cytokine functions, illuminates pleiotropic effects of cytokines, expands our knowledge of activation states of each immune cell type, and provides a framework to deduce the roles of specific cytokines and cell-cell communication networks in any immune response.

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The record

Venue
Nature
Topic
Single-cell and spatial transcriptomics
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
Dr. Miriam and Sheldon G. Adelson Medical Research FoundationNational Human Genome Research InstituteNational Cancer InstituteNational Institutes of HealthNatural Sciences and Engineering Research Council of CanadaBroad Institute
Keywords
Immune systemCytokineBiologyCell typeT cellImmunologyCellCell biologyGenetics
Has abstract in OpenAlex
yes