First cell atlas of thymus could lead to new immune therapies

The first cell atlas of the thymus gland could help researchers develop new immune therapies to treat cancer and autoimmune disease, new studies show.

Cell atlases operate as in-depth reference maps of human cells to help scientists understand human health, and ultimately treat disease better.

Now, experts from Newcastle University, the Wellcome Sanger Institute and Ghent University have mapped thymus tissue through the human lifespan to understand how it develops and produces immune cells (T cells).

The thymus gland is essential for the body’s production of T cells – white blood cells that help fight infection and disease. T cells leave the thymus to enter the blood, then seek out and destroy invading bacteria and viruses, as well as cancerous cells. A thymus that is unable to develop properly can cause defective T cell generation, resulting in severe immune deficiencies and leaving people susceptible to infections.

More so, it can affect T cell regulation resulting in autoimmune diseases such as Type 1 diabetes. Though mature T cells have been well studied, the development of the human thymus a T cells within it is not fully understood.

The research has been published in the journal Science and could help scientists generate an artificial thymus, as well as engineering improved therapeutic T cells.

In particular, the thymus cell atlas has enabled researchers to identify new cell types and signals that tell immature immune cells how to develop into T cells.

The researchers used single cell technology to isolate and analyse around 200,000 individual cells from the developing thymus, alongside child and adult thymus tissue. They then looked at which genes were active in each individual cell, discovering new cell types in the process, and used those genes as tags to map each cell to its exact location in the thymus.

The thymus is an unusual organ as it is largest and most active in childhood, shrinking after puberty and almost disappearing by age 35. A better understanding into how it develops and then shrinks could increase our knowledge of ageing and how the immune system changes through life.

The atlas could help aid in understanding diseases that affect T cell development such as severe combined immunodeficiency (SCID), and will assist the Human Cell Atlas initiative, which is creating a Google map of the entire human body.

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.”