Featured Research

from universities, journals, and other organizations

Maintaining restraint in the face of danger

Date:
March 30, 2012
Source:
RIKEN
Summary:
A central regulator of the inflammatory response shows signs as an appealing target for therapies against autoimmune disease.

A central regulator of the inflammatory response shows signs as an appealing target for therapies against autoimmune disease.

Some bacterial infections trigger the formation of structures known as granulomas, which essentially quarantine compromised cells. "Infected macrophages get surrounded by other immune cells, such as T cells and neutrophils," explains Takashi Tanaka of the RIKEN Research Center for Allergy and Immunology in Yokohama. "This serves to wall off pathogens that resist destruction and limits their infection within a restricted area."

This response is generally beneficial but can lead to a harmful overreaction, especially in patients with autoimmune conditions, where the inflammatory response is not properly regulated. In collaboration with Tadashi Matsuda of Hokkaido University, Tanaka's group has now revealed a key regulatory checkpoint in the granuloma formation process, which might ultimately inform the development of more effective immunomodulatory drugs.

Historically, a subset of the immune system's helper T cells, called TH1 cells, has been associated with autoimmunity. Previous research by Tanaka demonstrated that a protein called PDLIM2 helps restrict production of these cells. More recently, other researchers identified a population of helper T cells called TH17 cells that also contribute to this process, although their role was unclear, so Tanaka sought to determine whether PDLIM2 regulates these cells as well.

His team found that mice lacking the gene encoding PDLIM2 formed many more granulomas in response to infection with Propionibacterium acnes bacteria, and that this process was dependent on the action of TH17 cells. In fact, the researchers showed that PDLIM2 directly inhibits the differentiation of CD4+ T cells into TH17 cells, as was previously demonstrated with TH1 development. This protein works by marking other proteins for rapid degradation. Tanaka and colleagues learned that PDLIM2 specifically promotes the destruction of STAT3, a signaling protein that switches on genes responsible for TH17 development. Without PDLIM2 constraining the formation of these pro-inflammatory cells, the immune response has the potential to spiral out of control.

This protein therefore appears to be a key safeguard against autoimmunity. "Recent studies suggest that TH1 and TH17 cell subsets are not mutually exclusive, but cooperatively induce inflammatory responses," says Tanaka. "Our work demonstrates that PDLIM2 can negatively regulate the development of both cells, and thus represents a useful new target for the treatment of human autoimmune and inflammatory diseases." Tanaka and colleagues now hope to better understand this protein's function by clarifying the regulatory factors that act upstream and downstream of PDLIM2, and by clarifying how this system influences other inflammatory processes, such as those observed in cases of asthma or during wound healing.


Story Source:

The above story is based on materials provided by RIKEN. Note: Materials may be edited for content and length.


Journal Reference:

  1. T. Tanaka, Y. Yamamoto, R. Muromoto, O. Ikeda, Y. Sekine, M. J. Grusby, T. Kaisho, T. Matsuda. PDLIM2 Inhibits T Helper 17 Cell Development and Granulomatous Inflammation Through Degradation of STAT3. Science Signaling, 2011; 4 (202): ra85 DOI: 10.1126/scisignal.2001637

Cite This Page:

RIKEN. "Maintaining restraint in the face of danger." ScienceDaily. ScienceDaily, 30 March 2012. <www.sciencedaily.com/releases/2012/03/120330081208.htm>.
RIKEN. (2012, March 30). Maintaining restraint in the face of danger. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2012/03/120330081208.htm
RIKEN. "Maintaining restraint in the face of danger." ScienceDaily. www.sciencedaily.com/releases/2012/03/120330081208.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
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