Message wise — The biochemist from the RUDN University and the Institute of Biomedical Chemistry was the first to use multiple sclerosis as an example to investigate how variants of the protein that controls T lymphocytes affect the development of autoimmune diseases. This will help find new approaches to treating autoimmune diseases. The results were published in cells.
Regulatory T lymphocytes (Tregs) play a central role in regulating the body’s immune response. They control the strength and duration of the immune response. They are the ones who have to stop the protective response. If this does not happen, an autoimmune disease develops. The maturation and development of Tregs is controlled by the FoxP3 protein. The gene encoding this protein can produce 4 different variations of FoxP3. How these variations affect Tregs and how they relate to autoimmune diseases is still unknown. The RUDN University biologist and colleagues from the Institute of Biomedical Chemistry and the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician VI Kulakov tracked how different FoxP3 variants are formed and how they affect the suppression of the immune response.
“T lymphocytes control the immune response and play a key role in the development of autoimmune diseases. Patients with such diseases have reduced numbers of Tregs or are unable to suppress lymphocytes. The reasons for this are not fully understood. FoxP3 is the “master protein” responsible for the maturation and activity of Tregs. The role and association of FoxP3 variants with autoimmune diseases have never been studied before,” said Dmitry Zhdanov, PhD, associate professor at the Department of Biochemistry at RUDN University.
Doctors conducted a study with 20 healthy people and 20 patients with the autoimmune disease multiple sclerosis. The authors studied participants from both groups and analyzed their blood samples to examine which of the four FoxP3 variants were produced in their bodies and how this affected Treg activity.
Patients with multiple sclerosis were more likely to develop truncated variants of FoxP3. In healthy patients, the full version was the most important. In the first case, Tregs suppressed immune cells less actively. Shortened versions with two sections removed also reduced the rate of T lymphocyte production. This is the first time that biologists have demonstrated the connection between different FoxP3 variants and individual Treg properties.
“We showed that shifting FoxP3 to full-length variants stimulates Treg activity. It can be assumed that, if further developed, this will form the basis of a new strategy for the treatment of autoimmune diseases,” said Dmitry Zhdanov, PhD, associate professor at the Institute of Biochemistry at RUDN University.