Study reveals how immune cells target different tissues

For the first time, researchers revealed the different molecular identities of important immune cells, called regulatory T cells, using unicellular genomics, in mouse and human non-lymphoid peripheral tissues such as skin and colon. Wellcome Sanger Institute researchers and their collaborators found that regulatory T cells had tissue-specific receptors and other adaptations, which allowed them to move about and stay in the right place in the body. In the future, this could allow us to understand how to target therapeutic cells to specific areas of the body, for targeted treatments of autoimmune diseases, for example.

Reported in Immunity (Feb. 5), the study showed that mouse regulatory T cells had several intermediate cell states, inside and between tissues. They also discovered patterns of similar gene activity in humans, revealing more detail than ever about how the immune system is regulated.

Regulatory T cells (Tregs) are a specialized type of immune cells that control the immune system. They dampen the immune response to control it and prevent the body from attacking its own tissues. These cells are found in lymphoid tissues such as lymph nodes and spleen, as well as in other non-lymphoid tissues of the body. Although some differences are known about the functioning of regulatory T cells in different tissues, the understanding of the "GPS system" that targets cells to a specific tissue of the body is limited.

To create a detailed image of T cells, researchers studied 35,000 individual cells from lymph nodes in healthy mice, spleen, skin and colon, comparing cells from different tissues. They used single-cell RNA sequencing to find out exactly which genes were activated in each cell. The researchers found that different tissues had different cell populations and revealed the changes that regulatory T cells undergo as they move from tissue to tissue.

Further badysis revealed that even within one and the same tissue, the cells varied considerably, with a continuum of cellular states and regulatory activities. They also discovered that, although the sequence of cell states is very similar when they migrate to different peripheral tissues such as skin and colon, the cells express on the surface of separate chemokine receptors acting as a satnav to guide them to specific tissues.

Tomas Gomes, the lead author of the Wellcome Sanger Institute, said, "This is the first time anyone has described the wide and varied spectrum of T-cell populations in peripheral tissues, and we can see that these cells share the same identity. central T regulatory cells, they are very different from one tissue to another, with different functions, and even express different receptors to guide them to a specific tissue.This helps us understand the regulation of the immune system to maintain it in a healthy balance. "

The researchers badyzed Tregs from tumor and non-tumor cells of mice in specific tissues and found that they had the same gene activities. By comparing mouse data with Tregs from the skin, colon and human blood, they discovered receptors and similar signaling molecules in humans.

Fiona Powrie from Oxford University said, "We now know that Tregs play a unique role in different tissues, some of which are distinct from their suppressive function, by revealing the common and distinct molecular signals that support different populations. This study provides a better understanding of how Tregs interact with their environment to promote tissue health throughout the body. "

Sarah Teichmann, corresponding author of the Wellcome Sanger Institute, said: "This is the most comprehensive study ever done on the sequencing of single-cell RNA regulatory tissue T cells. not only helps to understand the immune system in a tissue, it also allows researchers to learn how to manipulate potential future therapeutic T cells, to design them for specific locations in the body and to target the proper tissue needed. "

Provided by
Wellcome Trust Sanger Institute