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
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 | Newswise Science News
New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences
The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Physics and Astronomy
21.11.2017 | Life Sciences