A promising treatment target has been identified that could be used for immune system-related disorders such as type 1 diabetes.
US scientists have identified a way of improving T cell survival following exposure to a mutation of a gene called Gimap5.
Using GSK3 inhibitors, a protein regulated by the Gimap5 gene, scientists were able to restore normal immune cell function in laboratory experiments of cells taken from a patient with the gene mutation. The inhibitors also helped to prevent colitis and liver damage in a mouse model.
Now, researchers from the Cincinnati Children’s Hospital Research Foundation are optimistic that expanding this treatment option could have implications for type 1 diabetes.
“Therapeutically targeting this pathway may be relevant for treating people with Gimap5 mutations linked to autoimmunity in type 1 diabetes (T1D), systemic lupus erythematosus (SLE), or asthma,” said lead author Dr. Hoebe, Ph.D..
GSK3 inhibitors have previously been used to treat health conditions including Alzheimer’s disease and cancer. They are pivotal for maintaining T cell health and proliferation.
If GSK3 is prevented from activating, which occurs during mutations with the Gimap5 gene, it can cause DNA damage in expanding T cells, which affects their survival.
There are different types of T cell in the body that play a number of different roles. In autoimmune diseases, there is known to be an imbalance of too many killer T cells that are programmed to kill specific cells and not enough regulatory T cells which help to keep killer T cells from killing healthy cells.
To build on their findings, the researchers plan to investigate the relationship between Gimap5 mutations and GSK3 regulation on T cell malfunction in human patients with immune disease.
“We posit that GSK3-inhibitors will improve overall T-cell survival and function and may prevent/correct immune-associated sequelae observed in these patients,” said the researchers.
“We believe the use of GSK3 inhibitors to prevent or correct these type of immune-related diseases holds great potential.”
The study team is also exploring research into how successful a treatment GSK3 could be in treating preclinical mouse models of allergic lung disease and lupus.
The findings have been published online in the journal Nature Communications.

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