Scientists create first full map of human immune system connectivity

Good news! Amazing stuff! This is probably a game changer!

"The immune system is made up of specialised cells, some of which individually travel through the body to scan for signs of injury or disease. Once these cells detect a threat, they need to communicate the message to other cells in order to mount an effective immune response. One way this cell-​to-cell signalling is done is through proteins on the surfaces of cells that bind on to matching ‘receptor’ proteins on the surfaces of other cells.

Previously, scientists and clinicians only had an incomplete map of these receptor connections between all of the different types of immune cells in the body. ...
This research, published in Nature, includes the discovery of many previously unknown interactions that together shed light on the organisation of the body’s immune defences. ...
Creating this detailed map of the immune system has required years of technological advances to tackle a problem of this scale. Each immune cell may have hundreds of distinct surface proteins and receptors on it, and the interactions involving these proteins are often so transient that specialised methods had to be invented to make assembling an accurate map possible. ..."

From the abstract:

"The human immune system is composed of a distributed network of cells circulating throughout the body, which must dynamically form physical associations and communicate using interactions between their cell-surface proteomes. Despite their therapeutic potential, our map of these surface interactions remains incomplete. Here, using a high-throughput surface receptor screening method, we systematically mapped the direct protein interactions across a recombinant library that encompasses most of the surface proteins that are detectable on human leukocytes. We independently validated and determined the biophysical parameters of each novel interaction, resulting in a high-confidence and quantitative view of the receptor wiring that connects human immune cells. By integrating our interactome with expression data, we identified trends in the dynamics of immune interactions and constructed a reductionist mathematical model that predicts cellular connectivity from basic principles. We also developed an interactive multi-tissue single-cell atlas that infers immune interactions throughout the body, revealing potential functional contexts for new interactions and hubs in multicellular networks. Finally, we combined targeted protein stimulation of human leukocytes with multiplex high-content microscopy to link our receptor interactions to functional roles, in terms of both modulating immune responses and maintaining normal patterns of intercellular associations. Together, our work provides a systematic perspective on the intercellular wiring of the human immune system that extends from systems-level principles of immune cell connectivity down to mechanistic characterization of individual receptors, which could offer opportunities for therapeutic intervention."

Scientists create first full map of human immune system connectivity

First map of immune system connections reveals new therapeutic opportunities Researchers of the Wellcome Sanger Institute and ETH Zurich have created the first full connectivity map of the human immune system, showing how immune cells communicate with each other and ways to modulate these pathways in disease.

A physical wiring diagram for the human immune system (open access)

Fig. 1: A leukocyte receptor network by systematic protein interaction mapping.