Featured Research

from universities, journals, and other organizations

New pathway regulates immune balance and offers promising drug development target

Date:
September 21, 2010
Source:
St. Jude Children's Research Hospital
Summary:
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.

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.

Related Articles


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.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Guangwei Liu, Kai Yang, Samir Burns, Sharad Shrestha, Hongbo Chi. The S1P1-mTOR axis directs the reciprocal differentiation of TH1 and Treg cells. Nature Immunology, 2010; DOI: 10.1038/ni.1939

Cite This Page:

St. Jude Children's Research Hospital. "New pathway regulates immune balance and offers promising drug development target." ScienceDaily. ScienceDaily, 21 September 2010. <www.sciencedaily.com/releases/2010/09/100920135135.htm>.
St. Jude Children's Research Hospital. (2010, September 21). New pathway regulates immune balance and offers promising drug development target. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2010/09/100920135135.htm
St. Jude Children's Research Hospital. "New pathway regulates immune balance and offers promising drug development target." ScienceDaily. www.sciencedaily.com/releases/2010/09/100920135135.htm (accessed November 23, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, November 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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