Featured Research

from universities, journals, and other organizations

Shadow Proteins In Thymus May Explain How Immune System Gets To Know Its Own Body

Date:
October 11, 2002
Source:
Harvard Medical School
Summary:
Researchers at Joslin Diabetes Center, Harvard Medical School, and other institutions have identified the function of a protein, dubbed aire, that is critical to helping immune cells learn to recognize -- and avoid attacking -- the far-flung organs and tissues of the body. The protein appears to work by turning on in the thymus, which lies beneath the breast bone, the production of a wide array of proteins from the body's periphery. The discovery could shed light not only on how the healthy immune system develops tolerance to its own proteins but also how tolerance is lost, as it is in diabetes, rheumatoid arthritis, Crohn's disease and other autoimmune illnesses.

Boston (October 10, 2002) -- Researchers at Joslin Diabetes Center, Harvard Medical School, and other institutions have identified the function of a protein, dubbed aire, that is critical to helping immune cells learn to recognize -- and avoid attacking -- the far-flung organs and tissues of the body. The protein appears to work by turning on in the thymus, which lies beneath the breast bone, the production of a wide array of proteins from the body's periphery. The discovery could shed light not only on how the healthy immune system develops tolerance to its own proteins but also how tolerance is lost, as it is in diabetes, rheumatoid arthritis, Crohn's disease and other autoimmune illnesses.

"Our findings lead back to humans because they tell us about a very important mechanism for controlling autoimmunity," said Diane Mathis, a Harvard Medical School professor of medicine at Joslin. "At the same time, they may help us understand why people develop autoimmune diseases." The findings are reported in the Oct. 11 Science.

Until recently, immune cells, in particular T cells, were thought to learn their most basic lesson -- attack foreign proteins but spare those that are native -- in one of two places. Those with a broad mandate, namely to monitor widely expressed cellular proteins or proteins circulating in the bloodstream, were thought to be trained to distinguish self from foreign proteins while still in the thymus. Cells that recognize proteins in organs and tissues in the periphery, such as the pancreas, thyroid, and adrenals, were believed to learn the self vs. non-self lesson once they left the thymus. This organ was thought incapable of producing proteins made by distant organs such as the liver, brain, and pancreas.

But it appears that T cells in training may be learning the lesson while still in the thymus.

Building on work of other groups, first author Mark Anderson, a research fellow in medicine at Joslin; Emily Venanzi, a Harvard Medical School graduate student in immunology; Christophe Benoist, a professor of medicine at Joslin; Mathis, and colleagues, reported that a small network of thymic cells -- the medullary epithelial cells -- expresses hundreds of genes usually associated with organs such as the pancreas, brain, and liver.

"No one would think you would encounter your big toe protein in the thymus, but in fact proteins from the eye, the liver, from all over the place are specifically expressed in a small population of stromal cells in the thymus," said Benoist.

A majority of these expressed proteins are used by the peripheral organs to tell T cells to stay away. Indeed, the researchers believe the proteins are used in the thymus to foreshadow the very self-antigens that the T cells will encounter once they travel out into the body.

"There is a foretelling of these proteins in the thymus, which is why we call it an immunological self-shadow," said Mathis.

In a critical step, the Joslin team discovered that the transcription factor aire plays a critical role in producing these self-shadow proteins in the thymus (hence its name, which is formed from two letters in each word of autoimmune regulator). Mutant mice lacking aire exhibited in their thymus only a fraction of the peripheral self-proteins found in the thymus of normal mice. And the mutants exhibited widespread autoimmunity. In fact, their condition was reminiscent of a condition found in humans carrying a defective AIRE gene, autoimmune polyglandular syndrome.

It is not yet clear how the shadow proteins educate developing T cells inside the thymus, though Benoist suspects the processes are similar to those used to eliminate T cells that react to ubiquitous or circulating proteins. Nor is it clear how aire controls the expression of so many shadow proteins. One possibility is that it works by binding to other transcription factors.

"It is going to be interesting to figure out what the mechanism really is," Mathis said. While novel, the mechanism is probably only one of many that the immune system uses to educate peripheral T cells about the self-vs.-foreign distinction.

"It is very dangerous for the immune system to have self-reactive T cells," Anderson said. "It takes advantage of any mechanism to get rid of these cells. So there is a whole net of mechanisms."

Other main collaborators on this study were Ludger Klein from the Dana-Farber Cancer Institute and Roderick Bronson from Harvard Medical School.


Story Source:

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


Cite This Page:

Harvard Medical School. "Shadow Proteins In Thymus May Explain How Immune System Gets To Know Its Own Body." ScienceDaily. ScienceDaily, 11 October 2002. <www.sciencedaily.com/releases/2002/10/021011071648.htm>.
Harvard Medical School. (2002, October 11). Shadow Proteins In Thymus May Explain How Immune System Gets To Know Its Own Body. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2002/10/021011071648.htm
Harvard Medical School. "Shadow Proteins In Thymus May Explain How Immune System Gets To Know Its Own Body." ScienceDaily. www.sciencedaily.com/releases/2002/10/021011071648.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
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