Researchers have discovered how the mutation of the Gimap5 gene affects the ability of T cells to stimulate immune disorders. The work was conducted under the supervision of the immunologist Kasper Hoba from the Children’s Medical Center of Cincinnati. The results of the experiments were published today in the journal Nature Communications.
The gene and protein Gimap5 are associated with the development and function of lymphocytes and the immune system, but in detail the mechanisms of their functioning by researchers have not yet been studied. It is known, for example, that Gimap5 plays an important role in the development of lymphopenia, a condition in which the body lacks lymphocytes. Lymphopenia can occur due to a variety of causes, such as inflammatory diseases, HIV, the taking of heavymedications and even pregnancy and stress.
To better understand the molecular mechanisms that cause failure of the immune system, the researchers focused on a gene mutation study Gimap5 that affects the healthy development and operation of T cells CD4 +; they play a key role in the immune system fight infections and various diseases. In the course of the experiments, the specialists found out that the Gimap5 protein regulates another protein that inactivates the enzyme called GSK3. The shortage or malfunction of Gimap5, and, as a consequence, activated GSK3 cause DNA damage in T cells, leading to their death or malfunction. The researchers also found that Gimap5 facilitates the phosphorylation of Ser389 and the nuclear translocation of GSK3β, thereby limiting DNA damage in CD4 + T cells.
All the experiments were carried out on a laboratory genetically modified mouse model, but a study of the biomaterial of a 16-year-old teenager with lymphopenia who agreed to participate in the work confirmed the data obtained in the laboratory. The author of the work noted that it is necessary to conduct additional studies before talking about the clinical significance of the data obtained for real patients. So far, according to Dr. Hoba, GSK3 inhibitors have the greatest potential.