Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tumor Suppressor Protein Is a Key Regulator of Immune Response and Balance

20.07.2011
St. Jude Children’s Research Hospital scientists have identified a key immune system regulator, a protein that serves as a gatekeeper in the white blood cells that produce the “troops” to battle specific infections.

Researchers demonstrated the protein, Tsc1, is pivotal for maintaining a balanced immune system and combating infections. Loss of the Tsc1 protein was associated with a reduction in the number of certain immune cells and a weaker immune response. The work appears in the July 17 online edition of the scientific journal Nature Immunology.

Scientists found that Tsc1 works by inhibiting the pathway that launches production of the specialized white blood cells known as effector T cells. Those cells are the backbone of the adaptive immune response, designed to respond, identify and destroy specific bacteria, viruses and other threats.

Working in mice with specially engineered immune systems, scientists showed Tsc1 also keeps cellular activity at a minimum in the white blood cells known as naïve T cells. That process is known as quiescence.

Quiescence has long been recognized as crucial to proper immune function. But until now scientists were unclear how quiescence was established and maintained in naïve T cells. “This study is the first to show that Tsc1 is a primary regulator of T cell quiescence,” said Hongbo Chi, Ph.D., assistant member St. Jude Department of Immunology, and the study’s senior author. The first author is Kai Yang, Ph.D., a postdoctoral fellow in Chi’s laboratory.

“These findings not only advance understanding of the cell biology of the immune system but also have great potential for clinical applications in the future,” Chi said. He speculated that the same process might also be important in regulating immune cells known as memory T cells that help the immune system recognize infectious agents encountered before and mount a rapid immune response.

Tsc1 is best known as a tumor suppressor, helping to prevent cancer development by inhibiting activity of the mTOR protein and the pathway that bears its name. The mTOR pathway plays a key role in cancer, metabolic disease and aging.

Now Chi and his colleagues demonstrated that in the immune system Tsc1 has a unique job. Through inhibition of the mTOR pathway, Tsc1 forces naïve T cells to maintain minimal metabolic and cellular activity. Normally that would only change when naïve T cells are activated and begin producing the more specialized effector T cells to combat a specific new threat.

In this study, scientists showed that loss of the Tsc1 protein predisposed affected T cells to premature activation, resulting in programmed cell death via the cell’s suicide pathway. Consequently, the process depleted the supply of T cells as well as another group of specialized immune cells known as invariant natural killer T cells. The loss also dampened the ability of mice to combat bacterial infections. “We think maintaining T cell quiescence is central to preventing premature cell death and ensuring a productive immune response,” Chi said.

Although more work is needed to understand mTOR regulation of T cell quiescence, this study offers a glimpse into the process. Tsc1 is part of a larger complex known to regulate mTOR activity. The mTOR protein is also a component in two larger complexes, known as mTORC1 and mTORC2. Chi and his colleagues demonstrated that naïve T cell quiescence requires Tsc1 to keep mTORC1 activity at a low level. If Tsc1 is lost or shut down prematurely, mTORC1 activity increases, leading to premature activation of the immune cells, which results in various abnormalities and cell death.

Other authors are Geoffrey Neale, Douglas Green, both of St. Jude; and Weifeng He, formerly of St. Jude.

The research was supported in part by the National Institutes of Health, the Arthritis Foundation, the Lupus Research Institute and ALSAC.

St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is internationally recognized for its pioneering research and treatment of children with cancer and other catastrophic diseases. Ranked one of the best pediatric cancer hospitals in the country, St. Jude is the first and only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. St. Jude has treated children from all 50 states and from around the world, serving as a trusted resource for physicians and researchers. St. Jude has developed research protocols that helped push overall survival rates for childhood cancer from less than 20 percent when the hospital opened to almost 80 percent today. St. Jude is the national coordinating center for the Pediatric Brain Tumor Consortium and the Childhood Cancer Survivor Study. In addition to pediatric cancer research, St. Jude is also a leader in sickle cell disease research and is a globally prominent research center for influenza.

Founded in 1962 by the late entertainer Danny Thomas, St. Jude freely shares its discoveries with scientific and medical communities around the world, publishing more research articles than any other pediatric cancer research center in the United States. St. Jude treats more than 5,700 patients each year and is the only pediatric cancer research center where families never pay for treatment not covered by insurance. St. Jude is financially supported by thousands of individual donors, organizations and corporations without which the hospital’s work would not be possible. For more information, go to www.stjude.org.

St. Jude Public Relations Contacts
Summer Freeman
(desk) 901-595-3061
(cell) 901-297-9861
summer.freeman@stjude.org
Carrie Strehlau
(desk) 901-595-2295
(cell) 901-297-9875
carrie.strehlau@stjude.org

Summer Freeman | Newswise Science News
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>