Link between gene mutations and immune disease discovered by researchers

Washington: According to a recent research, a group of scientists have found how a gene mutation affects T cell function to promote immune disorders.

The team then tested a treatment based on the discovery -- successfully fixing donated immune cells from a 16-year-old boy with an abnormally low level of white blood cells called lymphopenia.

The discovery centers on mutation of the gene Gimap5, which is important to the healthy formation and function of CD4+ T cells, one of the immune system's super soldiers against infection and disease.

Scientists noted that the protein associated with the Gimap5 gene (also Gimap5), is important because it regulates a protein that inactivates an enzyme called GSK3.

If GSK3 isn't inactivated it causes DNA damage in T cells that are expanding, causing the cells to not survive or function correctly.

In mice and human blood cells, the researchers tested drugs that inhibit GSK3, improving immune system function in mice and restoring normal T cell function in the human cells.

Study's lead author Kasper Hoebe, PhD, Division of Immunobiology, said, "Our data suggest GSK3 inhibitors will improve T cell survival and function and may prevent or correct immune-related disorders in people with Gimap5 loss-of-function mutations. Therapeutically targeting this pathway may be relevant for treating people with Gimap5mutations linked to autoimmunity in Type 1 diabetes, systemic lupus erythematosus or asthma."

The scientists associated with the current study said additional research is needed before the data have clinical relevance for patients.

Meanwhile, new experiments are underway to translate the findings into the clinic, Hoebe said. The scientists are investigating if and how genetic variants in Gimap5 affect GSK3 regulation causing malfunctioning T cells in patients with immune disorders.

They also are exploring the therapeutic potential of GSK3 inhibitors in preclinical mouse models of allergic lung disease and lupus to see if they can improve patient outcomes.

The study was published in journal Nature Communications.