Dictionary of immune responses to 86 cytokines <i>in vivo</i>at single-cell resolution

Abstract Cytokines mediate cell-cell communication in the immune system and represent important therapeutic targets. A myriad of studies have underscored their central role function, yet we lack a global view cellular responses each cell type to cytokine. To address this gap created Immune Dictionary – compendium single-cell transcriptomic profiles over 20 types response 86 cytokines murine lymph nodes vivo, representing 1,500 cytokine-cell combinations. cytokine-centric dictionary revealed that most induced highly type-specific responses. For example, inflammatory cytokine IL-1β distinct gene programs almost every type. type-centric identified multiple cytokine-driven polarization states type, including previously uncharacterized such as an IL-18-induced polyfunctional NK state. Based on dictionary, developed companion software, Response Enrichment Analysis (IREA), for assessing activities from expression data, applied it reveal networks tumors following checkpoint blockade therapy. Our generates new hypotheses functions, illuminates pleiotropic effects cytokines, expands our knowledge activation provides framework deduce roles specific any response. This work was supported by NIH Grant RM1HG006193 Adelson Medical Research Foundation N.H. also Natural Sciences Engineering Council Canada (NSERC) Doctoral Fellowship, Whitaker Health Fund Wellington Irene Loh Fellowship A.C., NCI Specialist Award (R50CA251956) S.L.