Researchers map the human immune system for first time

3 August 2022

A physical wiring diagram for the human immune system. Image courtesy of Nature.

Researchers have created the first complete map of the network of connections that make up the human immune system, showing how immune cells communicate with each other. 

The discovery could lead to new treatments for cancer, infectious diseases, and other conditions where immune responses play a role. 

The research, published in Nature, includes the discovery of many previously unknown interactions between immune cells across the body, shedding light on the organisation of the body's immune defences. 

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. 

An in-depth understanding of the interactions between immune cells, and how they communicate with the rest of  the human body as a whole, is vital if we are to develop treatments that enhance the immune system in order to fight disease. These treatments are known as immunotherapies. 

Immunotherapies have already demonstrated great potential in treating disease, most notably with certain cancers. However, these only work well in certain groups of patients and for particular conditions. Knowing the map of immune receptor connections could help explain why immunotherapies sometimes only work in a subset of patients, and offer new targets for designing future immunotherapies that may work for patients who currently do not benefit from these cutting-edge treatments. 

Senior author of the study, Professor Gavin Wright, Professor of Microbial Biochemistry, Hull York Medical School, University of York, said: "Immunotherapies work with the body’s immune system to combat diseases such as cancer and autoimmunity. They can be incredibly effective in certain groups of people, but not all, leaving some people without treatment.  

"Our research, a culmination of over two decades of work, could hold the key to understanding why these treatments are more effective in some groups, and how they could be adapted to ensure that as many people as possible can benefit from them." 

The study, led by the Wellcome Sanger Institute, details how the researchers isolated and investigated a near-complete set of the surface proteins that physically link immune cells together. They then used a large amount of computational and mathematical analysis to create a map showing the cell types, messengers, and relative speed of each conversation taking place between immune cells. 

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. 

With this map, it is possible to see the impact of different diseases on the immune system as a whole, and investigate new therapies that bind to different proteins on the immune cell surface. Cell surface proteins serve as the basis for new medicines more often than any other protein type, due to their accessibility to drugs and powerful influence on the signals a cell receives. 

Jarrod Shilts, first author from the Wellcome Sanger Institute, said: "Meticulously isolating and analysing every immune cell and their interactions with others has given us the first map of the conversations between all of the immune cells in the human body. This is a huge step in understanding the inner workings of the immune system and will hopefully be utilised by researchers all around the world to help develop new therapies that work with the body’s defence mechanisms." 

A physical wiring diagram for the human immune system is published in Nature. The research was funded by Wellcome and the Swiss National Science Foundation.  

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