Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study Suggests Breakthrough in Controlling T Cell Activation

14.05.2014

The discovery of a crucial mechanism that controls the activation of T cells, a blood cell whose primary job is to fight infection in the body, may enable the development of new drugs to treat autoimmune disease, transplant rejection, and similar disorders in which T cells play a major role. The finding, "T Cell Receptor Signals to NF-kB Are Transmitted by a Cytosolic p62-Bcl10-Malt1-IKK Signalosome," was published in the May 13 issue of Science Signaling.

A team of Uniformed Services University of the Health Sciences (USU) researchers led by Dr. Brian Schaefer, Associate Professor in USU’s Department of Microbiology and Immunology, has demonstrated that the “POLKADOTS signalosome” (named for its dot-like appearance in cells) activates a protein called “NF-kappaB” in T cells. A signalosome is a cluster of proteins that works together inside a cell to control the activity of other proteins. NF-kappaB is a protein that turns on many different T cell functions, including those that contribute to autoimmunity and rejection of transplants.

Dr. Schaefer’s team, including lead author, Dr. Suman Paul, had previously shown that the POLKADOTS signalosome, in addition to activating this protein, also limits how much NF-kappaB is turned on. Because the POLKADOTS signalosome is a major point of control for NF-kappaB activation, it may be an attractive target for the design of new drugs to block or regulate T cell functions.

Normally, T cells play a key role in maintaining health, by helping to eliminate invading disease-causing bacteria and viruses. However, in some individuals, T cells begin to react against tissues in the body, causing autoimmunity. Also, when a patient receives an organ transplant, T cells will react to that organ and cause transplant rejection, if T cell functions are not successfully blocked. There are currently only a small number of drugs available to treat autoimmunity and transplant rejection, and these drugs do not work for all patients.

Inhibiting NF-kappaB activation has long been recognized as a potentially useful strategy for blocking the T cell responses that cause autoimmunity and transplant rejection. However, because NF-kappaB is necessary for a wide variety of important processes throughout the body, directly targeting this protein would lead to many undesired and harmful side effects. Importantly, Dr. Schaefer’s group predicts that drugs that block the activity of the POLKADOTS signalosome would inhibit NF-kappaB only in T cells. This is because the POLKADOTS signalosome appears to be present only in T cells. If successfully produced, drugs that act on the POLKADOTS signalosome may be a powerful new therapy for the treatment of many different autoimmune diseases and transplant rejection.

This work was supported by grants from the U.S. NIH (Al057481), the Center for Neuroscience and Regenerative Medicine, and pre-doctoral fellowships from the American Heart Association (10PRE3150039) and the Henry M. Jackson Foundation for the Advancement of Military Medicine.

About USU
The Uniformed Services University of the Health Sciences, founded by an act of Congress in 1972, is the nation’s federal health sciences university and the academic heart of the Military Health System. USU students are primarily active duty uniformed officers in the Army, Navy, Air Force and Public Health Service who receive specialized education in tropical and infectious diseases, TBI and PTSD, disaster response and humanitarian assistance, global health, and acute trauma care. A large percentage of the university’s more than 5,000 physician and nearly 730 advanced practice nursing alumni are supporting operations around the world, offering their leadership and expertise. USU also has graduate programs in biomedical sciences and public health committed to excellence in research, and in oral biology. The University's research program covers a wide range of clinical and other topics important to both the military and public health. For more information about USU and its programs, visit www.usuhs.edu.

Sharon Willis | newswise
Further information:
http://www.usuhs.edu

Further reports about: Breakthrough Cell Controlling Health Medicine PTSD USU activation activity autoimmunity diseases drugs inhibit proteins rejection transplant

More articles from Life Sciences:

nachricht Fish Oil-Diet Benefits May be Mediated by Gut Microbes
28.08.2015 | University of Gothenburg

nachricht Bio-fabrication of Artificial Blood Vessels with Laser Light
28.08.2015 | Fraunhofer-Institut für Lasertechnik ILT

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: OU astrophysicist and collaborators find supermassive black holes in quasar nearest Earth

A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.

The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...

Im Focus: What would a tsunami in the Mediterranean look like?

A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).

Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...

Im Focus: Self-healing landscape: landslides after earthquake

In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.

These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...

Im Focus: FIC Proteins Send Bacteria Into Hibernation

Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.

For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...

Im Focus: Fraunhofer IPA develops prototype of intelligent care cart

It comes when called, bringing care utensils with it and recording how they are used: Fraunhofer IPA is developing an intelligent care cart that provides care staff with physical and informational support in their day-to-day work. The scientists at Fraunhofer IPA have now completed a first prototype. In doing so, they are continuing in their efforts to improve working conditions in the care sector and are developing solutions designed to address the challenges of demographic change.

Technical assistance systems can improve the difficult working conditions in residential nursing homes and hospitals by helping the staff in their work and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking conference in Heidelberg for outstanding mathematicians and computer scientists

20.08.2015 | Event News

Scientists meet in Münster for the world’s largest Chitin und Chitosan Conference

20.08.2015 | Event News

Large agribusiness management strategies

19.08.2015 | Event News

 
Latest News

Interstellar seeds could create oases of life

28.08.2015 | Physics and Astronomy

An ounce of prevention: Research advances on 'scourge' of transplant wards

28.08.2015 | Health and Medicine

Fish Oil-Diet Benefits May be Mediated by Gut Microbes

28.08.2015 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>