Immune cell migration is impeded in Huntington's disease

Huntington disease (HD) is an incurable neurodegenerative disease caused by a mutation in the huntingtin gene (htt). Though most of the symptoms of HD are neurological, the mutant HTT protein is expressed in non-neural cells as well.

In this issue of the , researchers led by Paul Muchowski at the J. David Gladstone Institutes in San Franscisco examined the role of immune cells in HD.

Immune cells known as microglia, which were isolated from the brains of HD mice, as well as immune cells from the peripheral blood were found to be defective in their ability to migrate.

Interestingly, the immune cell defects were apparent prior to the onset of HD symptoms.

This study suggests that changes in may underlie some of the symptoms of HD.

More information: Mutant huntingtin impairs immune cell migration in Huntington disease, Published in Volume 122, Issue 12 (December 3, 2012)
J Clin Invest. 2012;122(12):4737–4747. doi:10.1172/JCI64484

Abstract
In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.

add to favorites email to friend print save as pdf

Related Stories

Protecting the brain from a deadly genetic disease

Feb 23, 2010

Huntington's disease (HD) is a cruel, hereditary condition that leads to severe physical and mental deterioration, psychiatric problems and eventually, death. Currently, there are no treatments to slow down or stop it. ...

Research links huntingtin to neurogenesis

Aug 11, 2010

New research finds that a protein that is often mutated in Huntington's disease (HD) plays an unexpected role in the process of neurogenesis. The research, published by Cell Press in the August 12 issue of the journal Neuron, provid ...

Protein in Huntington's linked to neurogenesis

Sep 02, 2010

EU-funded scientists have discovered that a mutated protein inherent in Huntington's disease (HD) performs an unforeseen role in neurogenesis. The finding could lead to a better understanding of HD, an inherited ...

Recommended for you

Two expats die of MERS in Saudi commercial hub

8 hours ago

Two foreigners died of MERS in the Saudi city of Jeddah, the health ministry said Saturday, as fears rise over the spreading respiratory virus in the kingdom's commercial hub.

UAE reports 12 new cases of MERS

8 hours ago

Health authorities in the United Arab Emirates have announced 12 new cases of infection by the MERS coronavirus, but insisted the patients would be cured within two weeks.

Filipino tests negative for Middle East virus

20 hours ago

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

User comments