Newswise — The biochemist of RUDN University and Institute of Biomedical Chemistry was the first to study how variants of the protein that controls T-lymphocytes affect the development of autoimmune diseases using the example of multiple sclerosis. This will help find new approaches to the treatment of 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 must stop the protective reaction, and 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 V.I. Kulakov traced 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 a reduced number of Tregs or are unable to suppress lymphocytes. The reasons for this are not fully understood. FoxP3 is the “master protein” that is responsible for the maturation and activity of Tregs. The role and connection of FoxP3 variants with autoimmune diseases have never been studied before,” Dmitry Zhdanov, PhD, an Associate Professor at the Department of Biochemistry of RUDN University said.
Doctors conducted a study using 20 healthy people and 20 patients with the autoimmune disease multiple sclerosis. The authors examined participants in both groups and analyzed their blood samples, studying which of the 4 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-length version was the main one. In the first case, Tregs suppressed immune cells less actively. Shortened versions with two sections removed also reduced the rate of T-lymphocyte production. Thus, biologists have demonstrated for the first time the connection between different FoxP3 variants and individual Treg properties.
“We showed that shifting FoxP3 toward full-length variants stimulates Treg activity. It can be assumed that in case of further development, this will become the basis for a new strategy for the treatment of autoimmune diseases,” Dmitry Zhdanov, PhD, an Associate Professor at the Department of Biochemistry of RUDN University said.
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