Previously underexplored immune cell populations have been genetically mapped across multiple tissues to provide new insights into how our immune systems work.
The research, from the University of Cambridge, Wellcome Sanger Institute, and collaborators, has created an open-access atlas of the immune cells in the human body and focuses on those found within tissues, which are understudied, compared to those circulating in the blood.
This study is part of the international Human Cell Atlas (HCA) consortium, which is aiming to map every cell type in the human body as a basis for both understanding human health and for diagnosing, monitoring, and treating disease.
Developing immune cells (B cells) from prenatal gut tissue. Image credit: Chenqu Suo, Sophie Pritchard, Nadav Yayon (Wellcome Sanger Institute)
Published in Science, the research explores the similarities and differences of the same types of immune cells across 16 different tissues. Knowing more about immune cell traits and reactions in these tissues could help future research into therapies that aim to produce or enhance an immune response to fight disease, such as vaccinations or anti-cancer treatments.
It is one of a trio of milestone collaborative papers published together in Science, which have created comprehensive and openly available cross-tissue cell atlases. The complementary studies shed light on health and disease, and will contribute towards a single Human Cell Atlas.
The human immune system is made up of many different types of cells that can be found throughout the body, all playing crucial roles. They not only fight off pathogens when they appear, but remember them so they can be eliminated in the future.
In this new research, scientists simultaneously analysed immune cells across 16 tissues from 12 individual organ donors. The team developed a database that automatically classifies different cell types, called CellTypist, to handle the large volume and variation of immune cells. Through this, they were able to identify around 100 distinct cell types.
Using CellTypist and further in-depth analysis, the researchers created a cross-tissue immune cell atlas that revealed the relationship between immune cells in one tissue and their counterparts in others. They found similarities across certain families of immune cells, such as macrophages, as well as differences in others. For example, some memory T cells show unique features depending on which tissue they are in.
The team also uncovered new insights into immune system memory by sequencing the antigen receptors that are found on T and B cells. This part of the study showed the different states that T and B cells undergo if they are exposed to an antigen, such as those found on bacteria and viruses.
The wider research community can use this cross-tissue immune cell atlas to help interpret and inform future research. It could also serve as a framework to identify which immune cells could be useful to activate when designing new therapeutics that focus on guiding or supporting the immune system, such as vaccination and immunotherapies, for both infectious diseases and solid tumours.
Dr Cecilia Domínguez Conde, co-first author from the Wellcome Sanger Institute, said: “We have created a novel catalogue of immune cells within the human body, allowing us to automatically identify cell types across multiple tissues. By using single-cell sequencing data we have been able to reveal around a hundred different kinds of immune cells including macrophages, B cells, and T cells, uncovering crucial information about how the immune system works. We would like to thank the donors and their families for making this research possible.”
Dr Joanne Jones, co-senior author from the Department of Clinical Neurosciences at the University of Cambridge, said: “In this research, we not only identified distinct types of immune cells, we also found that certain immune cell types follow specific tissue distribution patterns. Understanding the varying behaviours of the same type of immune cell in multiple areas of the body can help inform research into disease and how treatments that target these cells might impact other tissues.”
Dr Sarah Teichmann from the Wellcome Sanger Institute and the Department of Physics at the University of Cambridge, co-founder of the Human Cell Atlas, said: “Our multi-tissue immune cell atlas is a step towards understanding how the immune system functions throughout the entire body and is an important contribution towards the Human Cell Atlas. In addition to creating a new resource for researchers to classify different cell types, our work will have many translational implications, including serving as a framework for developing therapies to fight immune-related diseases and managing infections.”
Source: Cambridge University