The STING of death in T cellsSeptember 05, 2017
The cells of the innate immune system use a signaling pathway comprising STING (Stimulator of interferon genes) to detect DNA from invading viruses and fight them. However, it is unknown if STING triggers the same or different responses in cells of the adaptive immune system, such as T cells. EPFL scientists have now shown that T cells have an "unconventional" STING response, which manifests as apoptotic cell death. The work, which may have implications for the treatment T cell-derived malignancies, is published in Nature Communications.
Innate immune system
The innate immune system is our first line of defense, made up of cells that quickly identify pathogens such as DNA from viruses. To do this, these cells use receptors that can identify nucleic acids -- the building blocks of DNA -- that in turn activate a signaling molecule called STING.
Once activated, the STING pathway turns on a set of genes that produce signaling molecules (cytokines) that help cells communicate with each other, as well as other cell-activating processes that fight off the infecting pathogen. But what we don't know whether the STING response produces different outcomes between different cell types.
The STING of death
The lab of Andrea Ablasser at EPFL looked at the consequences of the STING pathway in T cells. Their analysis found that STING triggers the expression of BH3-only proteins -- well known to be involved in cell death -- which induces apoptosis in cells, as opposed to the production of cytokines such as interferons, which stimulate immune responses.
Interestingly, the researchers also found that this pro-apoptotic effect exists in cancerous T cells, such as the ones that cause T-cell lymphomas, which account for about a tenth of non-Hodgkin lymphomas. The EPFL scientists found that delivering a small molecule that activates the STING pathway prevents the growth of T cell-derived tumors in live animals.
The work shows an unanticipated connection between the magnitude of STING signaling and its ability to elicit different responses. This may allow for cell-type-adjusted behaviors in the presence of internal or external insults such as infections or oxidative stress.
The study uncovers a novel, non-immune effect of the STING pathway whereby it induces a different effect in cells of the adaptive immune system (T cells) than its effect in cells of the innate immune system. The fact that this effect is pro-apoptotic and is maintained even in cancerous T cells in vivo open up significant possibilities for treating T-cell lymphomas in the future.
Medical University of Innsbruck
Tyrolean Cancer Research Institute
Swiss National Science Foundation
Novartis Foundation for medical-biological Research
Else Kröner Fresenius-Stiftung
Muhammet F. Gulen, Ute Koch, Simone M. Haag, Fabian Schuler, Lionel Apetoh, Andreas Villunger, Freddy Radtke, Andrea Ablasser. Signalling strength determines proapoptotic functions of STING. Nature Communications 05 September 2017. DOI: 10.1038/s41467-017-00573-w
Ecole Polytechnique Fédérale de Lausanne
Related Dna Articles:
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.
Related Dna Reading:
DNA: The Story of the Genetic Revolution
by James D. Watson (Author), Andrew Berry (Author), Kevin Davies (Author)
The definitive insider's history of the genetic revolution--significantly updated to reflect the discoveries of the last decade.
James D. Watson, the Nobel laureate whose pioneering work helped unlock the mystery of DNA's structure, charts the greatest scientific journey of our time, from the discovery of the double helix to today's controversies to what the future may hold. Updated to include new findings in gene editing, epigenetics, agricultural chemistry, as well as two entirely new chapters on personal genomics and cancer research. This is the most comprehensive and... View Details
The Family Tree Guide to DNA Testing and Genetic Genealogy
by Blaine T. Bettinger (Author)
Unlock the secrets in your DNA!
Discover the answers to your family history mysteries using the most-cutting edge tool available. This plain-English guide is a one-stop resource for how to use DNA testing for genealogy. Inside, you'll find guidance on what DNA tests are available, plus the methodologies and pros and cons of the three major testing companies and advice on choosing the right test to answer your specific genealogy questions. And once you've taken a DNA test, this guide will demystify the often-overwhelming subject and explain how to interpret DNA test results,... View Details
The Four: The Hidden DNA of Amazon, Apple, Facebook, and Google
by Scott Galloway (Author)
NEW YORK TIMES BESTSELLER
USA TODAY BESTSELLER
Amazon, Apple, Facebook, and Google are the four most influential companies on the planet. Just about everyone thinks they know how they got there. Just about everyone is wrong.
For all that’s been written about the Four over the last two decades, no one has captured their power and staggering success as insightfully as Scott Galloway.
Instead of buying the myths these companies broadcast, Galloway asks fundamental questions. How did the Four infiltrate our lives so completely that... View Details
Native American DNA: Tribal Belonging and the False Promise of Genetic Science
by Kim TallBear (Author)
Who is a Native American? And who gets to decide? From genealogists searching online for their ancestors to fortune hunters hoping for a slice of casino profits from wealthy tribes, the answers to these seemingly straightforward questions have profound ramifications. The rise of DNA testing has further complicated the issues and raised the stakes.
In Native American DNA, Kim TallBear shows how DNA testing is a powerful—and problematic—scientific process that is useful in determining close biological relatives. But tribal membership is a legal category that has... View Details
The Cosmic Serpent: DNA and the Origins of Knowledge
by Jeremy Narby (Author)
This adventure in science and imagination, which the Medical Tribune said might herald "a Copernican revolution for the life sciences," leads the reader through unexplored jungles and uncharted aspects of mind to the heart of knowledge.In a first-person narrative of scientific discovery that opens new perspectives on biology, anthropology, and the limits of rationalism, The Cosmic Serpent reveals how startlingly different the world around us appears when we open our minds to it. View Details
The Innovator's DNA: Mastering the Five Skills of Disruptive Innovators
by Jeff Dyer (Author), Hal Gregersen (Author), Clayton M. Christensen (Author)
A new classic, cited by leaders and media around the globe as a highly recommended read for anyone interested in innovation.
In The Innovator’s DNA, authors Jeffrey Dyer, Hal Gregersen, and bestselling author Clayton Christensen (The Innovator’s Dilemma, The Innovator’s Solution, How Will You Measure Your Life?) build on what we know about disruptive innovation to show how individuals can develop the skills necessary to move progressively from idea to impact.
By identifying behaviors of the world’s best innovatorsfrom leaders at Amazon and... View Details
DNA Science: A First Course, Second Edition
by David Micklos (Author), Greg Freyer (Author)
This is the second edition of a highly successful textbook (over 50,000 copies sold) in which a highly illustrated, narrative text is combined with easytouse thoroughly reliable laboratory protocols. It contains a fully uptodate collection of 12 rigorously tested and reliable lab experiments in molecular biology, developed at the internationally renowned Dolan DNA Learning Center of Cold Spring Harbor Laboratory, which culminate in the construction and cloning of a recombinant DNA molecule. Proven through more than 10 years of teaching at research and nonresearch colleges and universities,... View Details
The DNA Restart: Unlock Your Personal Genetic Code to Eat for Your Genes, Lose Weight, and Reverse Aging
by Dr. Sharon Moalem (Author), Nobu Matsuhisa (Foreword)
The DNA Restart turns traditional dietary advice on its head with groundbreaking research that demonstrates that we all require different diets based on our genes.
In The DNA Restart, Sharon Moalem, MD, PhD, provides a revolutionary step-by-step guide to the diet and lifestyle perfect for your individual genetic makeup. A physician, scientist, neurogeneticist, and New York Times bestselling author, Dr. Moalem has spent the last two decades researching and formulating how to reset your own genetic code using five essential pillars: eat for your genes; reverse... View Details
The Language of Life: DNA and the Revolution in Personalized Medicine
by Francis S Collins (Author)
"His groundbreaking work has changed the very ways we consider our health and examine disease.” —Barack Obama
From Dr. Francis Collins, director of the National Institute of Health, 2007 recipient of the Presidential Medal of Freedom, and 15-year head of the Human Genome Project, comes one of the most important medical books of the year: The Language of Life. With accessible, insightful prose, Dr. Collins describes the medical, scientific, and genetic revolution that is currently unlocking the secrets of “personalized medicine,” and offers practical advice on how to... View Details
Move Your DNA: Restore Your Health Through Natural Movement Expanded Edition
by Katy Bowman (Author)
Humorous, fascinating, and science based, the bestselling first edition of Move Your DNA has been updated and expanded to include a comprehensive three-level exercise program.
In layperson-friendly terms Move Your DNA addresses the vast quantities of disease we are suffering from, identifying our lack of movement as the primary cause. Readers can use the corrective exercises and lifestyle changes Katy Bowman has created to help each of us transition to healthy, naturally moving bodies. Move Your DNA explains the science behind our need for natural movement right down... View Details