Dictionary of immune responses to cytokines at single-cell resolution

Area of Science:

• Immunology
• Systems Biology
• Computational Biology

Background:

• Cytokines are key mediators of immune cell communication and therapeutic targets.
• A comprehensive understanding of cytokine-induced cellular responses is lacking.
• Existing knowledge lacks a global view of how diverse immune cells respond to specific cytokines.

Purpose of the Study:

• To create a comprehensive resource detailing single-cell transcriptomic responses of multiple immune cell types to numerous cytokines.
• To identify cell-type-specific cytokine responses and novel immune cell polarization states.
• To develop tools for analyzing cytokine activity and immune cell polarization from gene expression data.

Main Methods:

• Generated single-cell transcriptomic profiles for over 17 mouse immune cell types exposed to 86 cytokines in vivo.
• Compiled data into the Immune Dictionary, encompassing >1,400 cytokine-cell type combinations.
• Developed the Immune Response Enrichment Analysis software for data interpretation.

Main Results:

• Identified highly cell-type-specific responses to most cytokines, with examples like interleukin-1β.
• Discovered over 66 cytokine-driven cellular polarization states, including novel states in natural killer cells.
• Applied the analysis tool to reveal cytokine networks in tumor microenvironments after immune checkpoint blockade.

Conclusions:

• The Immune Dictionary provides a global view of cytokine-immune cell interactions, revealing cell-specific responses and novel activation states.
• The developed software facilitates the analysis of cytokine activity and immune cell polarization, aiding research in immunology and disease.
• This work offers a framework for investigating cytokine functions, pleiotropy, and cell-cell communication networks in various immune contexts.