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!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
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...
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...
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,...
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...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy