Molecular mechanism behind autoimmune diseases found

Scientists have discovered a new molecular mechanism behind some autoimmune diseases, an advance that may pave the way for new treatments against conditions caused by hyperactive immune systems.
While the immune system is crucial for protecting the body from infection and disease, prolonged activation can damage healthy tissue.
After its activation, the immune system is shut off by specialised immune cells known as regulatory T cells (Treg cells), researchers said.
Understanding the development of Treg cells is thought to be critical for combating autoimmune diseases.
"The development of Treg cells in the thymus depends on super-enhancer establishment," said Shimon Sakaguchi from Osaka University in Japan.

This super-enhancer establishment permits the expression of genes specific for Treg cell development.

"Super-enhancers appeared to be a pre-requisite for Treg cell development, so we sought molecules controlling super-enhancers," said Sakaguchi.
Researchers report that Satb1 regulates the super enhancers essential for Treg cell development.
Looking at the Treg cell development pathway, the scientists found that the level of Satb1 was highest before Treg cells develop, and dropped after Treg cell development.
Further study showed that Satb1 bound to the super enhancers responsible for Treg cell development, but again, only in progenitors that differentiated into Treg cells and not Treg cells themselves.

Therefore, Satb1 may regulate the epigenetic changes that precede the creation of Treg cells.
"Satb1 appears to be necessary for the differentiation of Treg cells, but not for the maintenance of Treg cells," said Yohko Kitagawa from Osaka University.
Indeed, in mice lacking Satb1, the development of Treg cells was impaired and the mice showed symptoms of autoimmune disease.
Furthermore, the progenitors cells of these mice showed inferior super enhancer activity, which resulted in less expression of the genes necessary for Treg cell development.
Based on these findings, Sakaguchi theorises that defective Satb1-dependent super-enhancer establishment could be a cause of autoimmune diseases and allergy.

"Autoimmune diseases are due to hyperactive immune systems. One cause is not having enough Treg cells. Understanding how this occurs is an important step towards treating autoimmune diseases," he said.
The study appears in the journal Nature Immunology.