(Press-News.org) Activation of beta-catenin, the primary mediator of the ubiquitous Wnt signaling pathway, alters the immune system in lasting and harmful ways, a team of Chicago-based researchers demonstrate in the February 26, 2014, issue of Science Translational Medicine.
An increase in beta-catenin in certain types of T cells—a class of white blood cells—causes chronic inflammation in the intestine and colon, eventually leading to cancer. The same mechanism is used by colon cancer to propagate itself. The researchers combine data from patients suffering from colitis or colon cancer with studies in mouse models of the disease to unravel the mechanism of this transition.
"We initially focused on this process in mouse models of hereditary colon cancer (polyposis), but the breakthrough came when we went to see patients," said the study's principal investigator, Fotini Gounari, PhD, associate professor of medicine at the Gwen Knapp Center for Lupus and Immunology Research at the University of Chicago. "Biopsied tissues from colitis patients contained T cells with high levels of beta-catenin. When we examined blood from colon-cancer patients, we found the same pathway activated in both conventional T cells and regulatory T cells."
Previous work by the team showed that a subset of protective T cells known as regulatory T cells, or Tregs—which normally stifle inflammation—switches functions in colon cancer patients to promote inflammation and enhance tumor growth.
The current study points to beta-catenin as the primary culprit. The researchers found mounting levels of this protein in T cells from patients with long-lasting ulcerative colitis and colon cancer. When Gounari and colleagues genetically engineered mice so that their T cells expressed high levels of beta-catenin, those mice were highly susceptible to colon cancer.
The finding "was a revelation," Gounari said. Activation of this signaling pathway appears to be an initiating event for colon cancer, which is then fed by uncontrolled inflammation in the tumor environment.
Normally, inflammation in the gut is elevated through the action of T-helper 17 (TH17) cells and suppressed by Tregs. This balance is important for keeping microbes in the gut at bay and for stimulating growth of cells during tissue repair. However, in colon cancer, a distinct set of regulatory T cells that have pro-inflammatory properties, expands rapidly and upsets the balance.
"We now have evidence that beta-catenin is a key molecule for expansion of both TH17 cells and pro-inflammatory Tregs," Gounari said.
With their unique mouse models, Gounari and colleagues were able to tease apart some of the mechanisms that generated pro-inflammatory T cells. They found that beta-catenin signaling initiated a cascade of events in both conventional T cells and Tregs that altered the chromatin organization and the type of genes expressed by T cells. These changes activate a protein called RORγT that was previously known to direct the differentiation of TH17 cells.
"It's like a tsunami," said collaborating partner, Khashayarsha Khazaie, PhD, professor of immunology at the Mayo Clinic. "If you make both your conventional T cells and Tregs pro-inflammatory, then you've done it. You've lost control in a bad way."
Understanding the process will provide ways to intervene in many diseases, the authors suggest.
"We want to disrupt the signals," Gounari said. "There are inhibitors under development that block RORγt or selectively interrupt the Wnt pathway in T cells. If you could block the pathway enough to tip the balance back to normal, that could potentially stop inflammatory bowel diseases and help control colon cancer."
"Activation of beta-catenin in T cells is unlikely to be restricted to these diseases, and is likely to happen in other autoimmune diseases and cancers, so there may be broad prospects for therapy of a range of chronic and often lethal diseases," she adds.
There is still work to be done, the researchers emphasize. They hope to learn more about how beta-catenin produces chromatin changes that disturb normal immune function, how this system interacts with the microbiome, and to determine the best targets for therapy.
But they have taken an important step. "Elucidating the molecular mechanisms that shift the lymphocyte balance from anti-inflammatory to proinflammatory," they wrote, "is expected to improve diagnosis and treatment of autoimmune diseases and cancer."
INFORMATION:
The paper, "β-Catenin Promotes Colitis and Colon Cancer through Imprinting of Pro-Inflammatory Properties in T Cells," will be published online on 26 February. Funding for this study was provided by the National Institutes of Health, the American Cancer Society, and the Circle of Service award from the Lurie Comprehensive Cancer Center.
Additional authors include co-first authors Shilpa Keerthivasan and Katayoun Aghajani, as well as Marei Dose, Luciana Molinero, Christopher Weber, Akinola Olumide Emmanuel and Tianjao Sun of the University of Chicago; Mohammad W. Khan, Vysak Venkateswaran, David J. Bentrem, Mary Mulcahy, Nichole Blatner and Elena M. Ramos of Northwestern University; and Ali Keshavarzian of Rush University Medical Center.
Beta-catenin alters T cells in lasting and harmful ways
Study helps explain chronic inflammation in autoimmunity and cancer
2014-02-26
ELSE PRESS RELEASES FROM THIS DATE:
Hubble monitors supernova in nearby galaxy M82
2014-02-26
This is a Hubble Space Telescope composite image of a supernova explosion designated SN 2014J in the galaxy M82. At a distance of approximately 11.5 million light-years from Earth it is the closest supernova of its type discovered in the past few decades. The explosion is categorized as a Type Ia supernova, which is theorized to be triggered in binary systems consisting of a white dwarf and another star — which could be a second white dwarf, a star like our sun, or a giant star.
Astronomers using a ground-based telescope discovered the explosion on January 21, 2014. This ...
Characterization of stink bug saliva proteins opens door to controlling pests
2014-02-26
Brown marmorated stink bugs cause millions of dollars in crop losses across the United States because of the damage their saliva does to plant tissues. Researchers at Penn State have developed methods to extract the insect saliva and identify the major protein components, which could lead to new pest control approaches.
"Until now, essentially nothing was known about the composition of stink bug saliva, which is surprising given the importance of these insects as pests and the fact that their saliva is the primary cause of feeding injury to plants and crop losses," said ...
New data book outlines Hispanic/Latino health
2014-02-26
The National Heart, Lung, and Blood Institute, part of the National Institutes of Health, released the largest and most comprehensive health and lifestyle analysis of people from a range of Hispanic/Latino origins. The data will enable individuals, communities, and policy makers to tailor better health intervention strategies.
"This study lays the foundation for future research on the possible causes of chronic diseases and ways to prevent them, and to help us understand the reasons why Hispanics and Latinos live longer than the general population," said Gregory Talavera, ...
Research maze puts images on floor, where rodents look
2014-02-26
PROVIDENCE, R.I. [Brown University] — A rodent in a maze is a staple — even a stereotype — of experimental psychology research. But the maze in the lab of Rebecca Burwell, professor of cognitive, linguistic, and psychological sciences at Brown University, is not your grandfather's apparatus. In a new video article published in the Journal of Visualized Experiments, Burwell's research group demonstrates in full detail how the maze can be used to perform automated visual cognitive research tasks with great efficiency.
The article is available here: http://www.jove.com/video/51316/automated-visual-cognitive-tasks-for-recording-neural-activity-using
The ...
Mayo Clinic discovers African-Americans respond better to rubella vaccine
2014-02-26
ROCHESTER, Minn. — Feb. 26, 2014 — Somali Americans develop twice the antibody response to rubella from the current vaccine compared to Caucasians in a new Mayo Clinic study on individualized aspects of immune response. A non-Somali, African-American cohort ranked next in immune response, still significantly higher than Caucasians, and Hispanic Americans in the study were least responsive to the vaccine. The findings appear in the journal Vaccine.
"This is fascinating," says Gregory Poland, M.D., Mayo Clinic vaccinologist and senior author of the study. "We don't know ...
JILA physicists discover 'quantum droplet' in semiconductor
2014-02-26
BOULDER, Colo -- JILA physicists used an ultrafast laser and help from German theorists to discover a new semiconductor quasiparticle—a handful of smaller particles that briefly condense into a liquid-like droplet.
Quasiparticles are composites of smaller particles that can be created inside solid materials and act together in a predictable way. A simple example is the exciton, a pairing, due to electrostatic forces, of an electron and a so-called "hole," a place in the material's energy structure where an electron could be, but isn't.
The new quasiparticle, described ...
Pine forest particles appear out of thin air, influence climate
2014-02-26
Pine forests are especially magical places for atmospheric chemists. Coniferous trees give off pine-scented vapors that form particles, very quickly and seemingly out of nowhere.
New research by German, Finnish and U.S. scientists elucidates the process by which gas wafting from coniferous trees creates particles that can reflect sunlight or promote cloud formation, both important climate feedbacks. The study is published Feb. 27 in Nature.
"In many forested regions, you can go and observe particles apparently form from thin air. They're not emitted from anything, ...
A predictive fitness model for influenza
2014-02-26
Researchers at Columbia University and the University of Cologne have created a new model to successfully predict the evolution of the influenza virus from one year to the next. This advance in our understanding of influenza suggests a new, systematic way to select influenza vaccine strains. The findings appear in Nature on Feb. 26.
The flu is one of the major infectious diseases in humans. Seasonal strains of the influenza A virus account for about half a million deaths per year. In a concerted effort, WHO and its Collaborating Centers have closely monitored the evolution ...
Sunburns strike twice
2014-02-26
Melanoma is particularly dangerous because it can form metastases in vital organs such as the lungs, liver or brain. UV radiation is considered to be the most significant triggering factor. An interdisciplinary team of researchers from the University Hospital and the LIMES Institute of the University of Bonn has now discovered that sunburns contribute to the development of this malignant disease not only through direct alteration of pigment cell genomes but also indirectly through inflammatory processes in the surrounding tissue. The results are now being published online ...
Major enigma solved in atmospheric chemistry
2014-02-26
According to their results, these extremely low-volatile organic compounds consist of relatively large molecules which contain an almost equal number of carbon, oxygen, and hydrogen atoms. The scientists present a plausible explanation supported by numerous experimental findings of how these vapours are formed almost immediately when plant emissions (e.g. monoterpenes) are released into the air. The vapours can then condense on small aerosol particles (starting from clusters of only a few nanometres in diameter) suspended in the air, causing them to grow to around 100 nanometres ...
LAST 30 PRESS RELEASES:
Sea surface temperatures and deeper water temperatures reached a new record high in 2024
Connecting through culture: Understanding its relevance in intercultural lingua franca communication
Men more than three times as likely to die from a brain injury, new US study shows
Tongue cancer organoids reveal secrets of chemotherapy resistance
Applications, limitations, and prospects of different muscle atrophy models in sarcopenia and cachexia research
FIFAWC: A dataset with detailed annotation and rich semantics for group activity recognition
Transfer learning-enhanced physics-informed neural network (TLE-PINN): A breakthrough in melt pool prediction for laser melting
Holistic integrative medicine declaration
Hidden transport pathways in graphene confirmed, paving the way for next-generation device innovation
New Neurology® Open Access journal announced
Gaza: 64,000 deaths due to violence between October 2023 and June 2024, analysis suggests
Study by Sylvester, collaborators highlights global trends in risk factors linked to lung cancer deaths
Oil extraction might have triggered small earthquakes in Surrey
Launch of world’s most significant protein study set to usher in new understanding for medicine
New study from Chapman University reveals rapid return of water from ground to atmosphere through plants
World's darkest and clearest skies at risk from industrial megaproject
UC Irvine-led discovery of new skeletal tissue advances regenerative medicine potential
Pulse oximeters infrequently tested by manufacturers on diverse sets of subjects
Press Registration is open for the 2025 AAN Annual Meeting
New book connects eugenics to Big Tech
Electrifying your workout can boost muscles mass, strength, UTEP study finds
Renewed grant will continue UTIA’s integrated pest management program
Researchers find betrayal doesn’t necessarily make someone less trustworthy if we benefit
Pet dogs often overlooked as spreader of antimicrobial-resistant Salmonella
Pioneering new tool will spur advances in catalysis
Physical neglect as damaging to children’s social development as abuse
Earth scientist awarded National Medal of Science, highest honor US bestows on scientists
Research Spotlight: Lipid nanoparticle therapy developed to stop tumor growth and restore tumor suppression
Don’t write off logged tropical forests – converting to oil palm plantations has even wider effects on ecosystems
Chimpanzees are genetically adapted to local habitats and infections such as malaria
[Press-News.org] Beta-catenin alters T cells in lasting and harmful waysStudy helps explain chronic inflammation in autoimmunity and cancer