Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Shadow proteins in thymus - Clues to how immune system works?

11.10.2002


Findings could lead to new understanding of diabetes, Crohn’s, and more



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.-nonself 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," she 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."

Marge Dwyer | EurekAlert!

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>