The study, recently published online ahead of print by the journal Blood, shows that disabling a particular enzyme, called ItpkB, in mice improves the function of a type of immune cell called Natural Killer cells.
“This is an exciting finding because it could possibly lead to the development of drugs that improve Natural Killer cell function,” said TSRI Associate Professor Karsten Sauer, PhD, who led the study. "Natural Killer cells have gained clinical interest as innovative biological therapeutics for certain cancers and also in certain infectious diseases.”
The Body’s ‘SWAT Team’
Natural Killer cells patrol the body and detect characteristic alterations on the surface of cancer cells or virus-infected cells. Through a complicated and little understood signaling machinery—a domino effect of molecular reactions in a cell that ultimately produces a certain signal—Natural Killer cells then destroy such ”stressed” cells.
Compared to other types of immune cells, Natural Killer cells kill these cells quickly. This makes Natural Killer cells important early responders of the immune system. Not surprisingly, researchers have explored engaging this "SWAT team" of the body therapeutically, particularly in blood cancers.
However, to date, the therapeutic efficacy of Natural Killer cells has been limited. “A key bottleneck is our limited understanding of signaling mechanisms that dampen Natural Killer cell function,” Sauer said.
Sauer and colleagues’ new research reveals crucial details of this puzzle.
A Way to Prime the Attack
The Sauer group had previously identified ItpkB as a key regulator of immune function. ItpkB acts primarily by producing IP4, a small molecule messenger that controls the functions of various other important signaling molecules. IP4 can improve or inhibit signaling depending on the cell type in which it is produced.
The new research showed that Natural Killer cells from mice lacking ItpkB show elevated signaling and function better than Natural Killer cells that have the enzyme. As a result, mice lacking ItpkB are more effective than mice expressing ItpkB in attacking cells that display characteristic surface changes of cancer cells.
“The enzyme ItpkB has unique features that facilitate its highly specific inhibition by small molecules,” said Sauer. "Our findings suggest that such compounds could possibly be used to improve Natural Killer cell function therapeutically. If successful, this could overcome a bottleneck and engage the body's SWAT team to fight cancer."
In addition to Sauer, Eugene Park of Washington University School of Medicine was a co-first author of the study, "Inositol Tetrakisphosphate Limits NK Cell Effector Functions by Controlling Phosphoinositide 3-Kinase Signaling.” Other authors include Sabine Siegemund, Luise Sternberg and Stephanie Rigaud of TSRI and Anthony R. French, Joseph A. Wahle, A. Helena Jonsson, Wayne M. Yokoyama and co-corresponding author Yina H. Huang of Washington University School of Medicine. For more information, see http://bloodjournal.hematologylibrary.org/content/early/2012/11/20/blood-2012-05-429241.abstract.
The research was supported by grants from the National Institutes of Health (AI070845, GM088647, AI089805 and AI007606), The Leukemia and Lymphoma Society Scholar Award 1440-11 and Deutsche Forschungsgemeinschaft fellowship SI 1547/1-1.
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, TSRI has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
Office of Communications
Mika Ono | Source: EurekAlert!
Further information: www.scripps.edu
More articles from Health and Medicine:
Primary care: strengthening the health system's first port of call
17.05.2013 | European Health Forum Gastein
Study Finds Plasmin—Delivered Through A Bubble—More Effective Than Tpa In Busting Clots
16.05.2013 | University of Cincinnati Academic Health Center
Researchers have shown that, by using global positioning systems (GPS) to measure ground deformation caused by a large underwater earthquake, they can provide accurate warning of the resulting tsunami in just a few minutes after the earthquake onset.
For the devastating Japan 2011 event, the team reveals that the analysis of the GPS data and issue of a detailed tsunami alert would have taken no more than three minutes. The results are published on 17 May in Natural Hazards and Earth System Sciences, an open access journal of ...
A new study of glaciers worldwide using observations from two NASA satellites has helped resolve differences in estimates of how fast glaciers are disappearing and contributing to sea level rise.
The new research found glaciers outside of the Greenland and Antarctic ice sheets, repositories of 1 percent of all land ice, lost an average of 571 trillion pounds (259 trillion kilograms) of mass every year during the six-year study period, making the oceans rise 0.03 inches (0.7 mm) per year. ...
About 99% of the world’s land ice is stored in the huge ice sheets of Antarctica and Greenland, while only 1% is contained in glaciers.
However, the meltwater of glaciers contributed almost as much to the rise in sea level in the period 2003 to 2009 as the two ice sheets: about one third. This is one of the results of an international study with the involvement of geographers from the University of Zurich.
Second sound is a quantum mechanical phenomenon, which has been observed only in superfluid helium.
Physicists from the University of Innsbruck, Austria, in collaboration with colleagues from the University of Trento, Italy, have now proven the propagation of such a temperature wave in a quantum gas. The scientists have published their historic findings in the journal Nature.
Below a critical temperature, certain fluids become superfluid ...
Researchers use synthetic silicate to stimulate stem cells into bone cells
In new research published online May 13, 2013 in Advanced Materials, researchers from Brigham and Women's Hospital (BWH) are the first to report that synthetic silicate nanoplatelets (also known as layered clay) can induce stem cells to become bone cells without the need of additional bone-inducing factors.
Synthetic silicates are made ...
17.05.2013 | Physics and Astronomy
17.05.2013 | Physics and Astronomy
17.05.2013 | Physics and Astronomy
17.05.2013 | Event News
15.05.2013 | Event News
08.05.2013 | Event News