Featured Research

from universities, journals, and other organizations

How cellular guardians of the intestine develop

Date:
August 21, 2014
Source:
Rockefeller University
Summary:
New research sheds light on the development of a unique class of immune cells known as intraepithelial lymphocytes found in the thin layer of tissue lining the intestine. This work may help lead to new insights into inflammatory diseases of the gut, including Inflammatory Bowel Disorder and celiac disease, as well as cancer.

Patrolling the border: New research explains the development of IELs, immune cells that inhabit the thin lining of the intestine. Above, transverse cross sections of the fingerlike villi of the intestine show green IELs within blue epithelial cells that border each villus.
Credit: Image courtesy of Rockefeller University

Even the most careful chosen meal can contain surprises. To defend against infectious microbes, viruses or other potential hazards that find their way to the intestines, a dedicated contingent of immune cells keeps watch within the thin layer of tissue that divides the contents of the gut from the body itself.

New research at Rockefeller University sheds light on the development of a unique class of immune cells known as intraepithelial lymphocytes (IELs) that reside in this critical interface. The findings, published August 21 in Immunity, may help lead to new insights on inflammatory diseases of the gut, including Inflammatory Bowel Disorder and celiac disease, as well as cancer.

"IELs can originate directly from an organ known as the thymus, or they are induced from other, fully mature lymphocytes. Our research has uncovered the pathway necessary for the generation of both so-called natural and induced IELs," says study author Daniel Mucida, assistant professor and head of the Laboratory of Mucosal Immunology. "The discovery of this pathway makes it possible to explore exactly how the IELs protect the gut, which no one has so far been able to address in a conclusive way."

IELs police the single-cell layer of intestinal epithelium, a fine boundary that spans as much as 400 square meters and allows nutrients in and wastes out. Nearly all IELs belong to a group of lymphocytes (themselves a type of white blood cell) known as T cells, produced by the thymus, an organ below the breastbone.

IELs are made one of two ways. "Natural" IELs require no additional activation after they are produced by the thymus. "Induced" IELs, meanwhile, are produced when two types of mature T cells, CD4 and CD8 cells, acquire new traits and move into the gut epithelium, becoming IELs.

During an immune response, CD4 cells send out signals to other immune cells, earning them the name helper T cells. In research published last year, Mucida and his colleagues uncovered how CD4 cells lose much of their helper function, and take on characteristics more commonly associated with CD8 cells and IELs, which are less likely to promote inflammation.

The new research took a closer look at this pathway, which the team had since determined leads to all IELs, natural and induced. They focused on two proteins, T-bet and Runx3, transcription factors that regulate the expression of genes. Both T-bet and Runx3 occur in high levels in IELs, and were already known to play a role in the development and function of T cells.

"Using genetically modified mice, along with other techniques, we determined the hierarchy between these two transcription factors: T-bet induces the expression of Runx3," says Bernardo Reis, a postdoc and first author of the study. "By exposing mature T cells from the blood to conditions like those in the gut, we found the gut environment itself may trigger this interplay and lead to the induction of IELs."

While these IELs, and the pathway leading to them, are crucial to intestinal health, they can sometimes malfunction and contribute to disease. For example, an unbalanced IEL response to gluten may lead to celiac disease, and reduced IEL function can also leave the intestine more vulnerable to infection.

"Now that we understand the IEL pathway and the genes involved, we can design studies that explore in more detail both IELs physiological, protective function and their detrimental side," Mucida says.


Story Source:

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


Journal Reference:

  1. BernardoS. Reis, DavidP. HoytemavanKonijnenburg, SergeiI. Grivennikov, Daniel Mucida. Transcription Factor T-bet Regulates Intraepithelial Lymphocyte Functional Maturation. Immunity, 2014; 41 (2): 244 DOI: 10.1016/j.immuni.2014.06.017

Cite This Page:

Rockefeller University. "How cellular guardians of the intestine develop." ScienceDaily. ScienceDaily, 21 August 2014. <www.sciencedaily.com/releases/2014/08/140821124833.htm>.
Rockefeller University. (2014, August 21). How cellular guardians of the intestine develop. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2014/08/140821124833.htm
Rockefeller University. "How cellular guardians of the intestine develop." ScienceDaily. www.sciencedaily.com/releases/2014/08/140821124833.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

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
CDC Calls for New Ebola Safety Guidelines

CDC Calls for New Ebola Safety Guidelines

AP (Oct. 20, 2014) Centers for Disease Control and Prevention Director Dr. Tom Frieden laid out new guidelines for health care workers when dealing with the deadly Ebola virus including new precautions when taking off personal protective equipment. (Oct. 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