Study reveals how immune cells transform to aid tissue healing after injury

Regulatory T cells (Treg cells) are a specialized subgroup of immune cells that play a central role in the human immune system. These cells can suppress erroneous and therefore harmful immune reactions that can lead to autoimmune diseases, for example. Furthermore, they actively promote the regeneration of tissue after injuries and thus orchestrate the wound healing process.

To this end, Treg cells can release tissue-healing substances and support regenerative cells such as tissue stem cells. They therefore cooperate with both immune and non-immune cells during tissue healing. These diverse functions make Treg cells attractive candidates for therapeutic use, for example, to promote tissue function after acute or chronic inflammation.

To support wound healing processes in the body, Treg cells must develop into so-called tissue-Treg cells. This development process is still poorly understood, and a better understanding is necessary to be able to use Treg cells in the treatment of diseases.

Scientists from the Division of Immunology at the LIT, in cooperation with scientists from the University Medical Center Mainz and the German Cancer Research Center, have now analyzed the differentiation process of Treg cells into tissue-Treg cells in humans in detail, deciphering so-called epigenetic changes in DNA in particular. Their study is published in the journal Nature Immunology.

“Epigenetics refers to changes in the way our genes function that do not involve a change in the actual DNA sequence itself. Instead, epigenetics is about ‘switches’ that are used to turn genes on or off, i.e., whether they are active and influence the function of a cell or not,” explains Prof. Charles Imbusch, one of the authors of the study.

These epigenetic changes are caused by chemical marks on the cell’s DNA, for example DNA methylation. During this process, a small molecule, the methyl group, is attached to certain sites on the DNA (so-called CpG sites). “If a gene at the CpG site near an ‘on’ switch is not marked with a methyl group, a gene can be activated,” describes Tamara Kaufmann, one of the authors of the study.

“It was also important for us not only to investigate DNA methylation at the approximately 28 million CpG sites, but also to relate our findings to other switch processes in Treg cells. In this way, we were able to provide comprehensive insights into how the specific function of tissue-Treg cells develop,” explains Dr. Niklas Beumer, one of the first authors of the study.

“The DNA methylation sites are the ‘genetic fingerprint’ of human tissue-Treg cells and they allow us to identify their specific properties,” says Prof. Delacher, one of the leaders of the study.

Decisive new insights were gained. “With this DNA methylation fingerprint of the tissue-Treg cells, we were able to identify tissue-Treg cells circulating in the blood. We also found many changes in so-called ‘jumping genes,'” describes Prof. Feuerer, one of the leaders of the study.

Jumping genes, also known as transposable elements, are pieces of DNA that can or once could move from one place in the DNA to another. For a long time, it was assumed that these “jumping genes” were non-functional. However, recent studies have shown that they play an important role in controlling gene activity, even though the vast majority of them are no longer mobile.

These research results show new ways and possibilities of how tissue-Treg cells could be used in the therapy of various diseases, such as promoting tissue function after severe inflammation or treating autoimmune disorders.