IFNg, produced by NK cells and other cell types, plays a critical role in killing pathogen-infected cells and in defending against tumor cells. However, overproduction of IFNg is also dangerous to the body and can cause autoimmune diseases. But exactly how the body tightly controls IFNg production – and, therefore, NK-cell activity – is not known.
The study, published in the May issue of the journal Immunity, looked at substances called pro-inflammatory cytokines, which cause NK cells to make IFNg and stimulate their activity. It also looked at transforming growth factor beta (TGFb), a substance also made by NK cells that lowers IFNg production.
The research, by investigators with the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, found that the pro-inflammatory cytokines not only cause NK cells to make IFNg, but they also shut down TGFb signaling, which inhibits production of IFNg.
That is, the cytokines not only increase some positive regulators of IFNg production, but they also shut down the TGFb signals that inhibit IFNg production.
In addition, the scientists found that TGFb turns down IFNg production – and, therefore, NK cell activity – both directly and indirectly.
The direct mechanism turns off the IFNg gene itself. The indirectly mechanism blocks a protein that normally turns up IFNg production.
“Our findings provide important details about the fine balance between positive and negative regulators of IFNg production in NK cells,” says principal investigator Michael A. Caligiuri, director of the OSU Comprehensive Cancer Center. “Mother Nature uses a symphony of cytokines that result in exquisitely tight control of its production in the healthy state.
“This might help us harness the cancer-killing ability of NK cells to control tumor growth and lead to new treatments that complement current cancer therapy,” he says.
The body carefully regulates IFNg levels. If there is too little of the substance, the risk of infection and cancer rises. If there is too much IFNg, NK cells become too plentiful and autoimmune diseases such as inflammatory bowel disease can occur.
“Our findings explain the yin and yang of the system that controls NK cells,” says first author Jianhua Yu, a post-doctoral student in Caligiuri’s laboratory. “When NK cells are called into action, the body not only turns up the activation pathway, it also shuts down the anti-activation pathway.”
Likewise, when TGFb turns down NK cell activity, it not only turns off the IFNg gene, it also shuts down the pathway that activates the gene.
“In each instance, these regulatory cytokines deliver a double whammy,” Caligiuri says. “They turn on what is needed and turn off anything that interferes with it.”
Funding from the National Cancer Institute supported this research.
Darrell E. Ward | EurekAlert!
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses