Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Pathway Regulates Immune Balance and Offers Promising Drug Development Target

22.09.2010
St. Jude Children’s Research Hospital scientists uncover a novel pathway for regulating T lymphocytes that play very different roles in inflammation. The mechanism offers a promising target for new drugs against autoimmune disorders.

St. Jude Children’s Research Hospital scientists have identified a new pathway that helps control the immune balance through reciprocal regulation of specialized T lymphocytes, which play very different inflammatory roles.

Investigators also determined that two drugs working in different ways to dampen the inflammatory response in patients with multiple sclerosis or following organ transplantation target this new mechanism. Further research into the pathway might lead to new medications to block other autoimmune disorders or to new anti-rejection drugs, researchers said. The work is published in the current online issue of Nature Immunology.

T cells are the white blood cells responsible for both driving and modulating the immune response. This work focuses on a mechanism at work as T cells differentiate into the more specialized T-helper 1 (Th1) cells that drive inflammation or the regulatory T cells that work to shut it down and protect healthy tissue from a misguided immune attack.

“The success or failure of the immune response requires T cells to make the right decision about their fate,” said Hongbo Chi, Ph.D., assistant member of the St. Jude Department of Immunology and the paper’s senior author.

“In this paper we describe the receptor that controls the cell fate determination of different subsets of T cells; controlling the choice to become either an inflammatory or a regulatory T cell,” Chi said. Earlier work from Chi and others linked the receptor, S1P1, to other aspects of T cell functioning.

Researchers also found surprising evidence T cell response is regulated by a lipid the T cell secretes rather than a protein known as a cytokine. If confirmed, Chi said the finding would mark the first time a lipid, rather than a protein, served such a signaling function in T cells.

For this study, investigators used both cultured cells and specially bred mice to link the S1P1 receptor to the fate of the two sub-groups of T cells. Stimulating S1P1 activates a pathway that drives the cell to become a pro-inflammatory Th1 cell. Th1 cells rally other immune components to act against infection and other threats. At the same time, S1P1 activation down regulates differentiation of regulatory T cells. The S1P1-dependent effect on both sub-groups of T cells relies on its ability to dampen signaling through another pathway in the T cell; this second pathway uses a different molecular route to influence the T cell’s fate, working through cytokine TGF-beta activation of a signaling molecule called Smad3.

“There is a reciprocal change between the two cell subsets. With this system, T cells that do not become regulatory T cells have a tendency to become T helper type 1 cells,” Chi said.

The S1P1 pathway is also targeted by the anti-rejection drug rapamycin, which is used to protect organ transplant patients, and FTY720, which has the promise to become the first oral therapy for use against relapsing multiple sclerosis. This study is the first to show both work in part by modulating this molecular pathway.

The work expands on earlier research from Chi’s laboratory showing the S1P1 receptor played a central role in inhibiting the development and function of regulatory T cells. “In this paper, we show that the receptor controls differentiation of conventional T cells as well,” he said, specifically Th-1 cells. S1P1 also plays a role in the movement of T cells throughout the body.

Researchers are now focused on understanding the pathways in more detail. The questions include how S1P1 activates the mTOR pathway. Once activated, mTOR, a protein kinase complex, works to dampen signaling along the TGF-Beta – Smad3 pathway, thereby promoting Th1 cell differentiation at the expense of regulatory T cells.

The paper’s co-first authors are Kai Yang of St. Jude and Guangwei Liu, formerly of St. Jude and currently of the Chinese Academy of Sciences. The other authors are Sharad Shrestha of St. Jude and Samir Burns, formerly of St. Jude.

This work 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 the No. 1 pediatric cancer hospital by Parents magazine and the No. 1 children’s cancer hospital by U.S. News & World Report, 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. In 2010, St. Jude was ranked the most trusted charity in the nation in a public survey conducted by Harris Interactive, a highly respected international polling and research firm. For more information, go to www.stjude.org.

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

More articles from Health and Medicine:

nachricht World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

nachricht Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern

All articles from Health and Medicine >>>

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 >>>