Immune System Connections Map Reveals Therapeutic Opportunities

Author: Wellcome Sanger Institute
Published: 2022/08/08 - Updated: 2024/09/11
Publication Details: Peer-Reviewed, Informative
Category Topic: Autoimmune Diseases - Academic Publications

Page Content: Synopsis - Introduction - Main

Synopsis: Researchers create a connectivity map of the human immune system showing how immune cells communicate with each other and ways to modulate these pathways in disease. An in-depth understanding of the interactions between immune cells and how this communication fits into the human body is vital if we are to develop treatments that enhance the immune system to fight disease, known as immunotherapies.

Defining Human Immune System

Human Immune System: The human immune system is a network of biological processes that protects an organism from diseases. It detects and responds to various pathogens, from viruses to parasitic worms, cancer cells, and objects such as wood splinters, distinguishing them from the organism's healthy tissue. The immune system protects your body from outside invaders. These include bacteria, viruses, fungi, and toxins (chemicals made by microbes). The immune system comprises different organs, cells, and proteins that work together. There are two main parts of the immune system: The innate immune system. You are born with this. The adaptive immune system. You develop this when your body is exposed to microbes or chemicals released by microbes. These two immune systems work together. Nearly all organisms have some kind of immune system.

Introduction

A first-of-its-kind comprehensive map of the network of connections that make up the human immune system has been created, which could lead to new immunotherapies to treat cancer, infectious diseases, and other conditions where immune responses play a role.

Main Content

In creating the immune system map, scientists from the Wellcome Sanger Institute, ETH Zürich, and collaborators show how immune cells across the body link up and communicate.

This research, published on 3 August 2022 in Nature, includes the discovery of many previously unknown interactions that together shed light on the organization of the body's immune defenses. This offers answers to longstanding questions about current immunotherapies that are already used to treat patients. In the future, this public and detailed immune system map could also be vital in identifying new therapies.

The immune system comprises specialized cells, some of which individually travel through the body to scan for signs of injury or disease. Once these cells detect a threat, they must communicate the message to other cells to mount an effective immune response. One way this cell-to-cell signaling is done is through proteins on the surfaces of cells that bind 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 the different types of immune cells in the body.

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Image showing immune cells - Image Credit: Yannik Severin, Julien Mena, Berend Snijder / ETH Zürich.

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An in-depth understanding of the interactions between immune cells and how this communication fits into the human body as a whole is vital if we are to develop treatments that enhance the immune system to fight disease, 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.

It is also necessary to understand the cell-to-cell signals in the immune system if we hope to prevent and treat autoimmune diseases, which are caused when the body mistakes internal signals and attacks itself.

This new publication, from the Wellcome Sanger Institute and collaborators, details how 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 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. The interactions involving these proteins are often so transient that specialized 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 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 cell signals.

"Meticulously isolating and analyzing 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 utilized by researchers all around the world to help develop new therapies that work with the body's defense mechanisms." - Jarrod Shilts, first author from the Wellcome Sanger Institute.

"This research has produced an incredible new tool that can be used to help highlight which proteins and pathways would be beneficial to target in drug development. It can also give insight into whether a drug will impact other pathways, which can cause side effects. All of this information may help in the development of new therapies and could give crucial supporting evidence to help ensure that the most effective treatments are put into clinical trials." - said Professor Berend Snijder, an author from the Institute of Molecular Systems Biology at ETH Zürich

"Immunotherapies work with the body's immune system to combat diseases such as cancer and autoimmunity. They can be incredibly effective in certain groups, 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." - Professor Gavin Wright, the senior author previously based at the Wellcome Sanger Institute and now at the University of York.

Publication:

J. Shilts, Y. Severin, F. Galaway, et al. (2022) A physical wiring diagram for the human immune system. Nature. DOI: 10.1038/s41586-022-05028-x

Funding:

This research was funded by Wellcome and the Swiss National Science Foundation.

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Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Wellcome Sanger Institute and published on 2022/08/08, this content may have been edited for style, clarity, or brevity.