Previously unknown immune cell types throughout development and adulthood have been identified, providing new insights into how the human immune system functions.
The Wellcome Sanger Institute, the University of Cambridge, and partners have published two new studies that provide open-access atlases of human immune cells. One research focuses on the immune system’s early development and the dispersion of immune cells throughout many organs. The other study examines immune cells in various organs from adults, giving a framework for cell-type identity prediction and insights into immunological memory.
These research projects are part of the international Human Cell Atlas (HCA) collaboration, which aims to map every cell type in the human body as a foundation for understanding human health and detecting, monitoring, and treating disease. HCA, an open, scientist-led consortium, is a global collaboration of academics, institutes, and funders, with more than 2,300 members from 83 countries.
Both findings, which were published in Science (May 12th, 2022), look at the similarities and differences of immune cells in various tissues, which have been understudied compared to those circulating in the blood. Knowing more about immune cell traits and behaviors in these tissues at different periods of life might help future research into vaccines and anti-cancer drugs that attempt to induce or strengthen an immunological response to fight disease.
These are two of four key research published this week in Science that resulted in comprehensive and freely accessible cross-tissue cell atlases. The complementing investigations will contribute to a single Human Cell Atlas and give information on health and disease.
The human immune system is made up of a variety of cells found throughout the body, all of which serve important roles. They not only fight pathogens when they arrive, but they also remember them so they may be eradicated later.
The Wellcome Sanger Institute and coworkers constructed a map of the developing human immune system across nine organs in the first study*. Researchers employed single-cell RNA sequencing and spatial transcriptomics to pinpoint the exact location of particular cells inside growing tissues.
Researchers discovered a novel form of B cell as well as distinct T cells that arise in the early stages of life. The researchers utilized data from another Human Cell Atlas study** to prove that these specific immune cells are not detected in adults.
This comprehensive atlas of human immune development reveals tissues involved in the formation of blood and immune cells, enhancing our understanding of immune and blood disorders. In cooperation with the other studies it enables mapping of the immune system from development to adulthood, revealing cell types that are lost as we grow up. It also helps to inform cell engineering and regenerative medicine research.”
Muzlifah Hannifa, Study First Senior Author and Professor, Wellcome Sanger Institute and Newcastle University
In the second study**, researchers from the Wellcome Sanger Institute at the University of Cambridge and its collaborators examined immune cells in 16 organs from 12 adult organ donors at the same time. To deal with the vast number and variety of immune cells, the team created CellTypist, a database, and algorithm that automatically identifies distinct cell types. Scientists were able to identify roughly 100 different cell types as a result of this.
The researchers built a cross-tissue immune cell atlas using CellTypist and additional in-depth analysis, revealing the link between immune cells in one tissue and their counterparts in other tissues. Researchers discovered similarities as well as variances in specific immune cell groups, such as macrophages. Some memory T cells, for example, have distinct characteristics depending on the tissue they are in.
We have created a catalog of immune cells within the adult 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 Cecilia Domínguez Conde, Study Second Co-First Author, Wellcome Sanger Institute
Dr Joanne Jones, from the University of Cambridge, is a co-senior author of the second study, “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 behaviors 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.”
These cross-tissue immune cell atlases are open to the public for use in interpreting and informing future research. A full cell atlas might be used to determine which immune cells to activate while developing novel treatments for infectious diseases and solid tumors that rely on directing or supporting the immune system, such as vaccination and immunotherapies.
Our multi-tissue immune cell atlases are a step towards understanding how the immune system functions throughout the entire body at different stages of life and are an important contribution towards the Human Cell Atlas. A detailed understanding of cells through the Human Cell Atlas will help explain many aspects of human health and disease.”
Dr Sarah Teichmann, Study Co-Senior Author, Wellcome Sanger Institute
Dr Sarah is also the Co-Founder of 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,” Dr Teichmann concluded.
Source:
Journal references:
- Suo, C., et al. (2022) Mapping the developing human immune system across organs. Science. doi.org/10.1126/science.abo0510.
- Conde, C. D., et al. (2022) Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science. doi.org/10.1126/science.abl5197.