Credit: Macmillan Publishers Limited

Technological advances have allowed researchers to provide, for the first time, a system-wide view of how immune cells exchange information. By measuring the proteomes and secretomes of all major human immune cell types, Felix Meissner and colleagues reveal new social networks and provide tantalizing details of intercellular signalling that are open to further investigation in a publicly accessible resource.

The authors used high-resolution mass spectrometry-based proteomics to characterize 28 primary human haematopoietic cell populations in the steady and activated states. For each major immune cell lineage, they identified an average of 9,500 proteins. These proteins were categorized (using principal component analysis) according to expression pattern and function. Cluster analysis recapitulated many known relationships of the immune system but it also provided new insights, such as an unexpectedly close relationship between natural killer (NK) cells and CD8+ effector memory T (TEM) cells. Their analysis also hinted at new cell lineage markers: CX3CR1 (CX3C-chemokine receptor 1) for CD8+CD45RA+ TEM cells, and PLVAP (plasmalemma vesicle-associated protein) and MEGF10 (multiple epidermal growth factor-like domains protein 10) for B cell-derived plasmablasts.

neutrophils and naive B cells were surprisingly well connected

To explore the intercellular communication networks, they compared receptor–receptor and ligand–receptor interactions (180,000 high confidence connections) between cell types and revealed several previously unknown interactions. For example, resistin, which is known to be secreted by monocytes, is also secreted by activated memory B cells. Myeloid cells had more connections than lymphoid cells, and neutrophils and naive B cells were surprisingly well connected despite their low relatedness. Interestingly, after activation, immune cells seem to use different communication strategies: antigen-presenting cells increase their capacity to send information, whereas cytolytic cell types increase their capacity to receive information. Finally, as a general underlying principle, for any given cytokine, communication was restricted to a limited number of sending and receiving cell types.

This rich resource of expression data can be considered a starting point towards a deeper understanding of the complexity of intercellular information exchange in the immune system.