Featured Research

from universities, journals, and other organizations

Breakthrough in controlling T cell activation

Date:
May 13, 2014
Source:
Uniformed Services University of the Health Sciences (USU)
Summary:
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 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.


Story Source:

The above story is based on materials provided by Uniformed Services University of the Health Sciences (USU). Note: Materials may be edited for content and length.


Journal Reference:

  1. S. Paul, M. K. Traver, A. K. Kashyap, M. A. Washington, J. R. Latoche, B. C. Schaefer. T Cell Receptor Signals to NF-B Are Transmitted by a Cytosolic p62-Bcl10-Malt1-IKK Signalosome. Science Signaling, 2014; 7 (325): ra45 DOI: 10.1126/scisignal.2004882

Cite This Page:

Uniformed Services University of the Health Sciences (USU). "Breakthrough in controlling T cell activation." ScienceDaily. ScienceDaily, 13 May 2014. <www.sciencedaily.com/releases/2014/05/140513091117.htm>.
Uniformed Services University of the Health Sciences (USU). (2014, May 13). Breakthrough in controlling T cell activation. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2014/05/140513091117.htm
Uniformed Services University of the Health Sciences (USU). "Breakthrough in controlling T cell activation." ScienceDaily. www.sciencedaily.com/releases/2014/05/140513091117.htm (accessed September 16, 2014).

Share This



More Health & Medicine News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Man Floats for 31 Hours in Gulf Waters

Man Floats for 31 Hours in Gulf Waters

AP (Sep. 16, 2014) A Texas man is lucky to be alive after he and three others floated for more than a day in the Gulf of Mexico when their boat sank during a fishing trip. (Sept. 16) Video provided by AP
Powered by NewsLook.com
EU Ministers and Experts Meet to Discuss Ebola Reponse

EU Ministers and Experts Meet to Discuss Ebola Reponse

AFP (Sep. 15, 2014) The European Commission met on Monday to coordinate aid that the EU can offer to African countries affected by the Ebola outbreak. Duration: 00:58 Video provided by AFP
Powered by NewsLook.com
Despite The Risks, Antibiotics Still Overprescribed For Kids

Despite The Risks, Antibiotics Still Overprescribed For Kids

Newsy (Sep. 15, 2014) A new study finds children are prescribed antibiotics twice as often as is necessary. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins