Year: 2025
Type: preprint
Abstract: Cytokines orchestrate immune responses, yet we still lack a comprehensive understanding of their specific effects across human immune cells due to their pleiotropy, context dependence and extensive functional redundancy. Here, we present a Human Cytokine Dictionary, created from high-resolution single-cell transcriptomes of 9,697,974 human peripheral blood mononuclear cells (PBMC) from 12 donors stimulated in vitro with 90 different cytokines. We describe donor-specific response variation and uncover robust consensus cytokine signatures across individuals. We then delineate similarities between cytokine response profiles, and derive cytokine-induced immune programs that organize responsive genes into data-driven, biologically interpretable functional modules. By integrating cell type-specific responses with expression of cytokines, we infer higher-order cell-to-cell and cytokine-to-cytokine communication networks exemplified by an IL-32-β-initiated signaling cascade, which rewires myeloid programs by inducing neutrophil-recruiting factors while suppressing Th1-responses and promoting IL-10-family cytokines. Finally, we show how the Human Cytokine Dictionary enables the interpretation of cytokine-driven immune responses in other studies and disease contexts, including systemic lupus erythematosus, multiple sclerosis, and non-small cell lung carcinoma. Together, the Human Cytokine Dictionary constitutes the first comprehensive cell type-resolved transcriptional screen of human cytokine responses and provides an essential open-access, easy-to-use community resource with accompanying software package to advance our understanding of cytokine biology in human disease and guide therapeutic discovery.
Source: Research Square
Authors: Fabian Theis, Lukas Oesinghaus, Sören Becker, Larsen Vornholz, Efthymia Papalexi, Joey Pangallo, Amir Moinfar, Jenni Liu, Alyssa La Fleur, Maiia Shulman, Simone Marrujo, Bryan Hariadi, Crina Curca, Alexa Suyama, Maria Nigos, Oliver Sanderson, Hoai Nguyen, Vuong Tran, Ajay Sapre, Olivia Kaplan, Sarah Schroeder, Alec Salvino, Guillermo Gallareta-Olivares, Ryan Koehler, Gary Geiss, Alexander Rosenberg, Charles Roco, Georg Seelig
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4417414129