Social Network Architecture of Human Immune Cells Unveiled by Quantitative Proteomics

The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not been established. Here, we applied high-resolution mass spectrometry-based proteomics to generate a publicly accessible protein atlas of 28 primary human immune cell populations in steady and activated states at a depth of > 10,000 proteins. Cell-type-specific protein copy numbers reveal that immune cells are most specialized at the level of ligands and receptors, thereby connecting distinct functions of the immune system. By integrating total and secreted proteomes, we deduce paracrine immune dynamics upon microbial encounter and discover fundamental intercellular communication structures as well as novel connections between cellular senders and receivers of biological information. Our comprehensive cell-type-resolved proteomic resource of human immune cells provides a framework for the orchestration of cellular interplay and a reference for altered communication associated with pathology.