Featured Research

from universities, journals, and other organizations

Deficient protein GM-CSF production found to impair gut's immune tolerance

Date:
March 13, 2014
Source:
Mount Sinai Medical Center
Summary:
The protein GM-CSF plays a critical role in maintaining immune tolerance in the gut, with defects in the protein increasing the susceptibility to inflammatory bowel diseases (IBD), according to a new mouse study. IBD is a severe intestinal disease characterized by chronic intestinal inflammation that results from a dysregulated immune response to microbes and food antigens.

The protein GM-CSF plays a critical role in maintaining immune tolerance in the gut, with defects in the protein increasing the susceptibility to inflammatory bowel diseases (IBD), according to a new mouse study by a team of researchers from the Icahn School of Medicine at Mount Sinai. IBD is a severe intestinal disease characterized by chronic intestinal inflammation that results from a dysregulated immune response to microbes and food antigens.

Writing in the peer reviewed journal Science published online March 13, 2014, the research team writes that this advances our understanding of how commensal microbes can regulate intestinal immunity and should pave the wave for identifying new drug targets.

“These results are highly relevant to clinical inflammatory bowel diseases because GMSCF-impaired function is now emerging as one of the best predictors of IBD severity,” said the study’s senior author, Miriam Merad, MD, PhD, Professor in the Department of Oncological Sciences, the Tisch Cancer Institute and the Immunology Institute, at the Icahn School of Medicine at Mount Sinai.

GM-CSF is a cytokine that promotes the development and function of a group of gut resident macrophages and dendritic cells. Although GMCSF is mostly known for its role in inflammation, Dr. Merad’s laboratory discovered that GM-CSF is produced in the normal gut by specialized cells called innate lymphocyte cells (ILCs) in response to microbiota signals. Strikingly, they found that microbiota-induced GM-CSF was required to imprint gut tissue resident macrophages and dendritic cells with regulatory function that was critical to protect against inflammation of the gut. Deletion of the GM-CSF gene in the mouse led to reduction and impaired regulatory function of gut tissue macrophages and dendritic cells which compromised induction of tolerance to food antigens and increased mice susceptibility to IBD.

“These results represent a significant advance in our understanding of how commensal microbes can regulate host intestinal immune responses and suggest that the identification of downstream targets in macrophages and dendritic cells along the GM-CSF axis can help the rationale design of novel strategies for the treatment of IBD patients with defective GM-CSF function,” explained Dr. Merad.

Drs. Merad and Mortha are now developing a multiscale approach to identify GM-CSF downstream targets using macrophages and dendritic cells isolated from GM-CSF deficient mice and exposed to recombinant GMCSF. The regulatory function of novel targets will be validated in collaboration with Judy H. Cho, MD, Ward-Coleman Professor of Medicine and Genetics and Genomic Sciences, and Assistant Chief of Research in the Gastrointestinal Division, and Jean Federic Colombel, MD, Professor of Medicine and Director of the Leona M. and Harry B. Helmsley Charitable Trust Inflammatory Bowel Disease Center, at they Icahn School of Medicine at Mount Sinai. They will study human macrophages and dendritic cells isolated from IBD patients with defective GM-CSF function, “The approach represents a step forward in personalizing how we treat patients with IBD,” said Dr. Colombel.


Story Source:

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


Journal Reference:

  1. A. Mortha, A. Chudnovskiy, D. Hashimoto, M. Bogunovic, S. P. Spencer, Y. Belkaid, M. Merad. Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis. Science, 2014; DOI: 10.1126/science.1249288

Cite This Page:

Mount Sinai Medical Center. "Deficient protein GM-CSF production found to impair gut's immune tolerance." ScienceDaily. ScienceDaily, 13 March 2014. <www.sciencedaily.com/releases/2014/03/140313142451.htm>.
Mount Sinai Medical Center. (2014, March 13). Deficient protein GM-CSF production found to impair gut's immune tolerance. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2014/03/140313142451.htm
Mount Sinai Medical Center. "Deficient protein GM-CSF production found to impair gut's immune tolerance." ScienceDaily. www.sciencedaily.com/releases/2014/03/140313142451.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

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
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. 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