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!
For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)
New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
27.06.2017 | Power and Electrical Engineering
27.06.2017 | Information Technology
27.06.2017 | Physics and Astronomy