Uncovering the Mechanisms Behind Autoimmune Diseases

Researchers have identified a new mechanism involved in the development of autoimmune diseases, and the findings may help develop new treatment options for conditions such as multiple sclerosis (MS).

Normally, regulatory T cells (Tregs) maintain immunological tolerance, by protecting harmless antigens from triggering an endogenous defensive reaction, as well as the body’s own structures in the case of inappropriately activated immune responses. Additionally, they prevent the development of allergies and autoimmune disorders.

Interleukin-(IL)17 producing T helper 17 (TH17) cells, play a large role in the development of MS. In healthy bodies, TH17 cells are responsible for the control of infecting fungi and bacteria.

However, these cells can also have an auto-aggressive effect where they are responsible for the destructive processes that occur during inflammation, and in many autoimmune diseases.

In the new study published in the Proceedings of the National Academy of Sciences (PNAS), researchers found that it is not only the ratio of Tregs to TH17 cells that decisively determine whether an autoimmune disorder develops or not, but also that the pharmacological inhibition of the protein kinase CK2 moves the balance of the 2 cell types towards Tregs.

During the study, researchers were able to demonstrate that the inhibition of CK2 resulted in a blockade of the signal pathways that TH17 cells require in order to evolve. On a molecular level, inhibiting CK2 lead to the inhibition of the signal pathways mediated by the cytokines interleukin-6, interleukin-21, and interleukin-23, and also those that regulate the gene expression through STAT3.

This results in the expression of the forkhead-box protein P3 (FOXP3) transcription factor, which controls the functioning and development of Tregs through genetic regulation. In the end, the auto-aggressive TH17 cells that are involved in the generation of autoimmune diseases become deprogrammed in cells, which protects the endogenous structures and stops the onset of autoimmune disorders.