New findings from St. Jude Children's Research Hospital reveal an unconventional control mechanism involved in the production of specialized T cells that play a critical role in maintaining immune system balance. The research appears in the current online edition of the scientific journal Nature.
The work focused on white blood cells known as regulatory T cells. These cells are crucial for a balanced immune response. Regulatory T cells suppress other immune system components in order to protect healthy tissue from misguided immune attacks or to prevent runaway inflammation.
St. Jude researchers showed that a molecular complex called mTORC1 uses an unconventional process to serve as a rheostat, controlling the supply and function of regulatory T cells. Loss of mTORC1 activity impairs the regulatory T cells that suppress the immune system's inflammatory response. The mTORC1 complex is part of the mTOR pathway, which was thought to inhibit rather than promote the number and function of regulatory T cells.
"These results challenge the prior view of the mTOR pathway as an inhibitor of these key immune cells and highlight the role of the mTORC1 complex in regulating the T cells that are vital for controlling inflammation," said Hongbo Chi, Ph.D., an associate member of the St. Jude Department of Immunology and the paper's corresponding author.
The findings also identified the mechanism mTORC1 uses in programming regulatory T cells to function as immune suppressors. Chi said the results should aid efforts to develop new drugs for use in organ transplantation or for treatment of autoimmune disorders.
For this study, researchers used specially bred mice to explore the mTOR pathway's role in the function of regulatory T cells. Investigators demonstrated mTORC1's importance by selectively deleting genes that carry instructions for making key elements of mTORC1 and a related complex. The deletion that targeted mTORC1 resulted in dramatically reduced immune suppression by regulatory T cells and the mice rapidly developed a fatal inflammatory disorder.
Researchers also showed that mTORC1 works by integrating signals from two immune receptors on the cell surface with cholesterol metabolism. With the right input, mTORC1 promoted production of regulatory T cells and cemented their role as suppressors of immune activity.
In another twist, investigators linked that suppressive function to cholesterol and lipid metabolism. Rather than relying on more conventional strategies of immune regulation, researchers showed how regulatory T cells depend on the metabolic pathway to control production of molecules CTLA4 and ICOS, which are responsible for immune suppression. Production of CTLA4 and ICOS by regulatory T cells decreased as lipid metabolism dropped. "We are just starting to appreciate the importance of lipids in the immune system, particularly in the function of regulatory T cells," Chi said.
Hu Zeng of St. Jude is the study's first author. The others are Kai Yang, Caryn Cloer, Geoffrey Neale and Peter Vogel, all of St. Jude.
The research was supported in part by grants (AR053573, AI094089, AI101407 and NS064599) from the National Institutes of Health, the Lupus Research Institute and ALSAC.
Summer Freeman | EurekAlert!
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy