Dictionary of immune responses to cytokines at single-cell resolution

• 成果类型: Article
• 署名作者: Cui, Ang; Huang, Teddy; Li, Shuqiang; Ma, Aileen; Perez, Jorge L.; Sander, Chris; Keskin, Derin B.; Wu, Catherine J.; Fraenkel, Ernest; Hacohen, Nir
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-7006
• DOI: 10.1038/s41586-023-06816-9
• 发表日期: 2024-01-11
• 页码: 377-384
• 关键词: transcriptional network; il-1 family; reconstruction; interferons; expression; spectrum; reveals; beta; tnf

摘要

Cytokines mediate cell-cell communication in the immune system and represent important therapeutic targets(1-3). A myriad of studies have highlighted their central role in immune function(4-13), 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-1 beta 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.