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 Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

nachricht Chlamydia: How bacteria take over control
28.03.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers create artificial materials atom-by-atom

28.03.2017 | Physics and Astronomy

Researchers show p300 protein may suppress leukemia in MDS patients

28.03.2017 | Health and Medicine

Asian dust providing key nutrients for California's giant sequoias

28.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>