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Dictionary of immune responses to cytokines at single-cell resolution

Ang Cui (), Teddy Huang, Shuqiang Li, Aileen Ma, Jorge L. Pérez, Chris Sander, Derin B. Keskin, Catherine J. Wu, Ernest Fraenkel and Nir Hacohen ()
Additional contact information
Ang Cui: Massachusetts Institute of Technology
Teddy Huang: Dana–Farber Cancer Institute
Shuqiang Li: Broad Institute of MIT and Harvard
Aileen Ma: Broad Institute of MIT and Harvard
Jorge L. Pérez: Broad Institute of MIT and Harvard
Chris Sander: Broad Institute of MIT and Harvard
Derin B. Keskin: Broad Institute of MIT and Harvard
Catherine J. Wu: Broad Institute of MIT and Harvard
Ernest Fraenkel: Broad Institute of MIT and Harvard
Nir Hacohen: Broad Institute of MIT and Harvard

Nature, 2024, vol. 625, issue 7994, 377-384

Abstract: Abstract Cytokines mediate cell–cell communication in the immune system and represent important therapeutic targets1–3. A myriad of studies have highlighted their central role in immune function4–13, 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.

Date: 2024
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DOI: 10.1038/s41586-023-06816-9

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