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!
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering