Featured Research

from universities, journals, and other organizations

Single MicroRNA Fine-tunes Innate Immune Response

Date:
February 24, 2008
Source:
Whitehead Institute for Biomedical Research
Summary:
A single microRNA, microRNA-223, in mice controls the production and activation of granulocytes, white blood cells essential for host defense against invading pathogens. Now, scientists have discovered the first microRNA shown to play a key role in the immune system's early warning system--the innate immune response.

Over the last few years scientists have discovered hundreds of microRNAs--tiny RNAs that regulate the expression of protein-coding genes. However, the functions of these novel molecules in mammals are largely unknown.

Now, scientists in the lab of Whitehead Fellow Fernando Camargo have discovered the first microRNA shown to play a key role in the immune system's early warning system--the innate immune response. The research reveals that microRNA-223 controls the production and activation of granulocytes, white blood cells essential for host defense against invading pathogens. The findings may have implications for the treatment of inflammatory conditions as well as leukemia.

"MicroRNA-223 is unique because its expression is entirely restricted to a specific branch of the immune system," says Camargo. "We found that microRNA-223 is crucial for the development and function of the innate branch of the immune system. Our work suggests that microRNA-223 physiologically fine-tunes both the generation and function of granulocytic cells, delimiting their production and dampening their activation."

The study indicated that microRNA-223 targets Mefc2, a transcription factor that promotes the expansion of granulocyte cell progenitors. (Transcription factors are proteins that regulate gene expression.) By knocking out Mefc2, the authors found that some of the effects caused by microRNA-223 were eliminated.

The researchers demonstrated that mice modified to lack microRNA-223 expression had up to three times as many granulocytes in their bone marrow and blood. Moreover, the granulocytes matured more rapidly and then reacted more aggressively to stimuli. This increased activity caused tissue inflammation and damage within the lungs with age or, in an acute inflammation model, within the liver, muscle and kidneys.

"If you have an infection in the lungs, granulocytes will migrate to the site of the infection and attack," says Jonathan Johnnidis, first author of the paper and a former technician in the Camargo lab, and now a graduate student in molecular biology at the University of Pennsylvania. "Once the infection is cleared granulocytes usually migrate away and settle down. However, in this case they didn't stand down after they were done fighting. Instead they continued an inflammatory response that did more damage."

"Like a hand grenade once you pop the trigger out, these granulocytes are going to explode, regardless of whether they are surrounded by healthy tissue or harmful bacteria," adds Camargo. "Lack of microRNA-223 makes it much easier to activate the grenade."

Camargo plans to further investigate the effect of this microRNA on disease. "Our work suggests that microRNA-223 physiologically fine-tunes both the generation and function of granulocytic cells, delimiting their production and preventing excessive activation," he says. "Also, since many forms of leukemia express diminished levels of microRNA-223, we are investigating how silencing of this microRNA may contribute to the development of that disease."

Fernando Camargo is a Fellow at Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted.

Whitehead Institute for Biomedical Research is a nonprofit, independent research and educational institution. Wholly independent in its governance, finances and research programs, Whitehead shares a close affiliation with Massachusetts Institute of Technology through its faculty, who hold joint MIT appointments.

Journal reference: Jonathan B. Johnnidis, Marian H.Harris, Robert T. Wheeler, Sandra Stehling-Sun, Michael H. Lam, Oktay Kirak, Thijn Brummelkamp, Mark D. Fleming and Fernando D. Camargo. "Regulation of progenitor cell proliferation and granulocyte function by microRNA-223" Nature, Volume 451, Number 781


Story Source:

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


Cite This Page:

Whitehead Institute for Biomedical Research. "Single MicroRNA Fine-tunes Innate Immune Response." ScienceDaily. ScienceDaily, 24 February 2008. <www.sciencedaily.com/releases/2008/02/080219113318.htm>.
Whitehead Institute for Biomedical Research. (2008, February 24). Single MicroRNA Fine-tunes Innate Immune Response. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2008/02/080219113318.htm
Whitehead Institute for Biomedical Research. "Single MicroRNA Fine-tunes Innate Immune Response." ScienceDaily. www.sciencedaily.com/releases/2008/02/080219113318.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
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