Much scientific attention is directed at understanding how this innate immune system is turned on, but little to how it is cooled down or regulated. That is important because the innate immune system is associated with inflammation. In turn, unchecked inflammation is associated with cancer, heart disease, autoimmune diseases and other chronic ailments.
A team of researchers led by Baylor College of Medicine has identified a protein called NLRC5, a member of the NOD-like protein family, that is involved in inhibition of protein complexes key to critical pathways of innate immunity called NF-êB and type I interferon signaling. A report on their work appears in the current issue of the journal Cell.
"Understanding the molecular mechanisms that hold innate immunity in check could provide clues to better treatments for cancer and autoimmune diseases associated with inflammation," said Dr. Rong-Fu Wang, professor in the Center for Cell and Gene Therapy, the department of pathology and immunology at BCM and a senior author of the report.
Think of the innate immune system as a rushing cascade, blocked in places by chunks of rock or landscape and forced through natural cavities in a particular direction. Protein complexes such as the protein IKK complex in NF-êB pathway, and RIG-I and MDA5 as pathogen sensors in type I interferon pathways, act like these natural forces to control and direct the cascade of events that result in innate immunity.
NLRC5 interacts with two subunits of IKK to prevent their activation through blocking addition of a phosphate molecule (phosphorylation). This in turn, inhibits NF-êB activation and innate immune responses. NLCRC5 also interacts with innate immune receptors RIG-I and MDA5 to block type I interferon response.
When Wang and his colleagues "knocked down" or reduced the amount of the NLRC5 protein, both NF-êB and type 1 interferon activity increased, resulting in increased innate immune responses and antiviral immunity.
"Our findings identify NLRC5 as a key negative regulator that blocks two central components of the NF-êB and type I interferon pathways," said Wang. That makes it a key element in keeping the innate immune system running at just the right level.
Others who took part in this research include Jun Cui, Liang Zhu, Xiaojun Xia, Helen Y. Wang, Xavier Legras, Jun Hong and Jiabing Ji, all of BCM, Pingping Shen of the College of Life Science at Nanjing University in China, Shu Zheng of Zhejiang University Medical School in Hangzhou, China and Zhijian J. Chen of The University of Texas Southwestern Medical Center in Dallas.
Funding for this work came from the National Cancer Institute, the National Institutes of Health, the China Scholarship council and the Howard Hughes Medical Institute.
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology