FEB 01, 2018 06:13 AM PST

Gimap5 Mutation Causes White Blood Cell Disorder

WRITTEN BY: Kara Marker

One gene mutation is responsible for disrupting the function of a key immune cell population involved in protecting the body from disease - and it can be fixed. From Cincinnati Children’s Hospital Medical Center, scientists have identified and successfully implemented a way around a genetic mutation responsible for multiple immune disorders.

This confocal microscopic image of a healthy mouse T cell uses color florescence to illustrate how the protein Gimap5 (faint green area) and the enzyme GSK3 (red) overlap. Credit: Cincinnati Children's Hospital

A gene and protein pair called Gimap5 is responsible for boosting immune function, promoting white blood cell survival, and T cell formation in the thymus. Gimap5 accomplishes these functions partly by inactivating an enzyme called GSK3. If a type of immune cell population called CD4+ T cells is expanding and GSK3 is still active, DNA damage, dysfunction, and death occurs for these T cells.

CD4+ T cells are a vital component of the adaptive arm of the immune system, which responds methodically and specifically to incoming infections. These T cells help B cells make antibodies, activate macrophages which, in turn, identify, engulf, and destroy foreign microorganisms, and recruit other immune cells to sites of infection and inflammation.

A mutation in Gimap5 prevents GSK3 from being inactivated, negatively impacting T cell function and contributing to multiple immune disorders, including immune deficiency (the body is ill-equipped to protect itself) and autoimmunity (the body mistakenly attacks its own cells as if they were foreign pathogens).

Past studies have linked genetic variations of Gimap5 with autoimmunity and colitis, but the present study is the first to demystify some of the mystery surrounding the biological mechanisms responsible for this link.

In mice and human blood cells, researchers tested the efficacy of drugs that inhibit GSK3 when Gimap5 is mutated and can’t inactivate GSK3 on its own. They saw that these drugs improved immune function in mice and T cell function in human cells.

"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," explained study co-leader Kasper Hoebe, PhD. "Therapeutically targeting this pathway may be relevant for treating people with Gimap5 mutations linked to autoimmunity in Type 1 diabetes, systemic lupus erythematosus or asthma."

The present study was published in the journal Nature Communications.

Sources: Blood, Cincinnati Children’s Hospital Medical Center

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
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