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.
You May Also Like
NOV 16, 2018
Technology
NOV 16, 2018
Novel 'Cellphone' Technology Detects HIV
Human immunodeficiency virus 1 (HIV), weakens the immune system by attacking healthy cells. Currently, the management of HIV remains a major global health ...
NOV 21, 2018
Immunology
NOV 21, 2018
Yin and Yang of Malaria
Researchers determine the affect of preventative treatment for malaria on infants...
DEC 05, 2018
Immunology
DEC 05, 2018
Combo-Kick to Battle Lymphoma
Combination immunotherapy has provided remission for patients suffering from Hodgkin's Lymphoma...
DEC 18, 2018
Health & Medicine
DEC 18, 2018
Mapping the Human Proteome
Advancing our understanding of human disease often requires a sound understanding of normal human physiology. A critical tool to provide guidance on human...
JAN 15, 2019
Immunology
JAN 15, 2019
Decipher the Clues with CRISPR
Scientists have created the first retroviral CRISPR-Cas9 gene editing library to explore the regulation of mouse T cells, which are key cells in the immune system. Researchers mapped the most...
JAN 23, 2019
Immunology
JAN 23, 2019
Can Old Cells Have Positive Impacts on MS Patients?
A new study shows that there is a very limited regeneration of cells in the brain of patients diagnosed with multiple sclerosis (MS)....
Loading Comments...