A first cell atlas of the human thymus gland could lead to new immune
therapies to treat cancer and autoimmune diseases. Researchers from the
Wellcome Sanger Institute, Newcastle University and Ghent University, Belgium,
mapped thymus tissue through the human lifespan to understand how it develops
and makes vital immune cells called T cells. In the future, this information
could help researchers to generate an artificial thymus and engineer improved
therapeutic T cells.
Published today (20 February) in Science, this human thymus atlas
has revealed new cell types and identified signals that tell immature immune
cells how to develop into T cells. The atlas could also help scientists
understand diseases that affect T cell development such as severe combined
immunodeficiency (SCID), and adds to the Human Cell Atlas initiative which is
creating a Google map of the entire human body.
The thymus gland
is located in the chest and produces T cells, key white blood cells that fight
infection and disease. These T cells then leave the thymus to enter the blood
and other parts of the body to mature further. T cells seek out and destroy
invading bacteria and viruses, and also recognise cancer cells and kill them.
Problems in
thymus development causes defective T cell generation. This can result in
severe immune deficiencies such as SCID, leaving people susceptible to
infections. Alternatively, it can affect T cell regulation resulting in
autoimmune diseases such as Type 1 diabetes. While mature T cells have been
well studied, the development of the human thymus and T cells within it is not
fully understood.
Researchers used
single cell technology to isolate and analyse around 200,000 individual cells
from the developing thymus, and child and adult thymus tissue. They looked at
which genes were active in each individual cell to identify the cells,
discovering new cell types, and used those genes as tags to map each cell to
its exact location in the thymus.
Dr Jongeun Park,
the first author on the study from the Wellcome Sanger Institute, said: “We
have produced a first human thymus cell atlas to understand what is happening
in the healthy thymus across our lifespan, from development to adulthood, and
how it provides the ideal environment to support the formation of T cells. This
openly available resource will allow researchers worldwide to understand how
the immune system develops to protect our body.”
Therapeutic T
cells are currently being used in the clinic to treat B-cell lymphoma and leukaemia
cancers, however a major drawback to these treatments is creating the right
subtype of T cells.
Professor
Muzlifah Haniffa, a senior author of the study from Newcastle University and
Senior Clinical Fellow at the Wellcome Sanger Institute, said: “With this
thymus cell atlas, we are unravelling the cellular signals of the developing
thymus, and revealing which genes need to be switched on to convert early
immune precursor cells into specific T cells. This is really exciting as in the
future, this atlas could be used as a reference map to engineer T cells outside
the body with exactly the right properties to attack and kill a specific cancer
— creating tailored treatments for tumours.”
Professor Tom
Taghon, a senior author of the study from Ghent University, Belgium, said: “We
now have a very detailed understanding of how T cells form in healthy tissue.
We have been able to identify a similar population of precursor cells in the
developing thymus and liver, and we believe that these precursors are important
for initiating T cell development in the fetus, and for the establishment of a
fully competent thymus organ. This is helping us put jigsaw pieces together to
get a bigger picture of how immunity develops.”
The thymus is
unusual in that it is largest and most active in childhood and shrinks after
puberty. The thymus has been called the ‘pacemaker of life’ and by age 35 has
almost disappeared. Understanding how the thymus develops and then withers
could cast light on aging and how the immune system changes through life.
Dr Sarah
Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of
the Human Cell Atlas Organising Committee, said: “This map of the thymus is an
important part of the Human Cell Atlas mission to chart every cell type in the
human body. It is helping us learn about developmental pathways within the
body, and the age-associated decline of the immune system. This has
applications in cellular engineering, including the possibility of creating an
artificial thymus for regenerative medicine.”
Journal article: https://science.sciencemag.org/content/367/6480/eaay3224
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