Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Nutrition Gene Key in Regulating Immune System

18.05.2005


A gene that signals a yeast cell to make bread rise and mice to eat a better diet also helps selectively silence the immune system, researchers have found.



The finding may help explain how a mother avoids rejecting a genetically foreign fetus and provides a new target for treatments to help the immune system ignore other desirables like a transplanted organ. “Think of this like a radio transmitter and a receiver,” says Dr. David H. Munn, pediatric hematologist-oncologist at the Medical College of Georgia and lead author of the study in the May issue of Immunity.

The transmitter is indoleamine 2,3-dioxygenase, or IDO, an enzyme particularly expressed in places such as the gastrointestinal tract and tonsils where the immune system routinely meets up with foreign substances it might want to ignore. Drs. Munn, Andrew L. Mellor and Simon J. Conway published a Science article in 1998 showing IDO’s role in protecting the fetus from rejection by the mother’s immune system during pregnancy. Later they learned that tumors and persistent viruses such as HIV may hijack this mechanism to shield themselves from immune attack. They knew IDO degraded tryptophan, an amino acid essential to the survival of T cells. They weren’t so certain what happened at the receiving end.


The researchers wondered if T cells exposed to IDO might simply starve to death without enough trytophan, one of nine essential amino acids attainable only through food. “If the T cells are just starving, then you don’t need a receiver. They just die. But the T cells didn’t seem to be dying. They seemed to be rendered selectively non-responsive,” says Dr. Munn. “That sounded more like the T cell was participating in this process.”

So the researchers started looking at the few genes known to respond to amino acid levels and found GCN2. GCN2 is present and active in many cells, but its major sites of action are unknown and its role in T cells was unexplored, Dr. Munn says. “GCN2 is a nutrition sensor in yeast,” says Dr. Munn. GCN2 helps yeast know when it has sufficient nutrition to grow; bread keeps rising until yeast run out of nutrition. A paper published in March in Science explores GCN2’s role in mammalian survival by enabling mice to sense they need to eat a well-balanced diet to stay healthy.

Dr. Munn contacted Dr. David Ron, a professor of medicine and cellular biology at New York University School of Medicine’s Skirball Institute, studying the nutritional aspects of the gene. Dr. Ron, a co-author on the Immunity paper, shared a GCN2 knockout mouse he developed and helped the MCG researchers study the gene’s role in T cells. When these knockout mice were exposed to IDO, their T cells simply ignored it. The researchers had found a receiver and possibly more.

“No one had known any gene specifically targeted by IDO, and now we have one,” says Dr. Munn. “We had not known how T cells were turned off. We didn’t know if the T cells just were never activated, or if they were actively suppressed by IDO. They all look like resting T cells. Now we do know that there are differences.”

MCG researchers want to know more about how GCN2 puts T cells to sleep. “Whatever it’s doing doesn’t appear to be killing the T cells. It would be nice to be able to mimic the effect of IDO by using a drug that activates this pathway.” Now that they have a knockout, comparative studies with regular mice can determine other genes that might be impacted downstream of GCN2.

Another big question is whether T cells deactivated by this system can be reactivated. Knowing the role of the GCN2 gene makes it easier for scientists to watch what happens to the T cells affected by IDO in a living organism. “We know that IDO itself is an important pathway. Evidence is emerging that IDO seems to contribute to several important regulatory processes in the immune system,” Dr. Munn says of findings from labs across the country. “But there has been a question in the field about how the IDO expressed in one cell can signal to neighboring T cells. Here’s our first evidence of one way it may do so. By giving you a target in the T cell that IDO is talking to, it helps you understand the system better and we think it also may give us another target for drugs to try to intervene in the system.”

The studies were funded by the National Institutes of Health and the Carlos and Marguerite Mason Trust.

Toni Baker | EurekAlert!
Further information:
http://www.mcg.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>