Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Nutrition Gene Key in Regulating Immune System


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:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>