Synthetic messenger boosts immune system

Fast, direct route: New signaling pathway discovered for T cell activation in the liver

2014-09-05

(Press-News.org) This news release is available in German.

When a pathogen attacks a healthy cell in the body, T lymphocytes are tasked with identifying and destroying the infected cell. Scientists know that they undergo a "training program" for this task in the lymph nodes or the spleen. "Programming cells" play a key role here, presenting pathogen constituents to the T lymphocytes. This is how the T lymphocytes learn to recognize these components and become specialized "killer" cells. Research teams led by Prof. Percy Knolle from Klinikum rechts der Isar and the University of Bonn and Prof. Stefan Rose-John from the University of Kiel have now discovered a second site where T lymphocytes can be programmed to attack pathogens.

The researchers identified the liver as an immunological organ where special tissue cells act as "programming cells" to prepare the T lymphocytes for their battle against infected cells. They were also able to decrypt the exact molecular code used by these tissue cells to equip the T lymphocytes with special infection-fighting capabilities. "This new mechanism is particularly interesting because the T cells are activated directly and very rapidly – in just 18 hours instead of 72," explains Percy Knolle.

Synthetic messenger as new adjuvant

The key to all this is a natural messenger from the interleukin family: IL-6/sIL-6R. It only becomes effective when the two individual components (IL-6 and sIL-6R) combine. Previously, scientists were only aware of a role for the substance in regeneration and the development of inflammatory responses. But now the research teams have shown that the T lymphocytes in the liver engage in direct contact with the "programming cells" found there, and that IL-6/sIL-6R very efficiently activates the T cells.

Once the researchers had uncovered this new mechanism, they were able to use a synthetic designer messenger developed by Stefan Rose-John, known as Hyper-IL-6, for the targeted stimulation of T lymphocytes. In this construct, the two individual components which are normally separated are directly and firmly linked to each other. "In combination with the familiar stimulation mechanisms of the T lymphocytes, Hyper-IL-6 can be used to effect a specific 'hyper stimulation' of T lymphocytes for particular therapeutic purposes. This could be an important step in helping us improve vaccine formulations," adds Percy Knolle.

As well as components of the pathogen, current vaccines also contain substances known as adjuvants. After a few intermediate steps, adjuvants indirectly activate the T lymphocytes and help to build up immunity. "We are placing high hopes on hyper-IL-6 as an effective new adjuvant capable of activating T cells directly and thus more rapidly. This could for example help us tackle chronic bacterial or viral infections which have not previously responded to vaccinations," he concludes.

INFORMATION: Original publication Böttcher J.P., Schanz O., Garbers C., Zaremba A., Hegenbarth S., Kurts C., Beyer M., Schultze J.L., Kastenmüller W., Rose-John S., and Knolle P.A., IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8+ T Cell Function, Cell Reports, 2014.
DOI: 10.1016/j.celrep.2014.07.008

Contact Prof. Dr. Percy Knolle
Institute of Molecular Immunology/Experimental Oncology
Klinikum rechts der Isar, Technische Universität München
Tel.: +49 (0)89 4140-6921
percy.knolle@tum.de
http://www.imi.med.tum.de

ELSE PRESS RELEASES FROM THIS DATE:

Combination microRNA therapy shown to suppress non-small-cell lung cancer

2014-09-05

BOSTON – Micro RNAs (miRNA) have recently emerged as key therapeutic agents against cancers and are actively being evaluated in pre-clinical models of various cancers as well as in human clinical trials. Now, new findings show that a combination therapy of two miRNAs, let-7 and miR-34, suppressed tumor growth in an animal model of non-small-cell lung cancer, offering a promising therapeutic avenue for this extremely aggressive malignancy. Currently reported online in the journal Oncogene, the study provides two important examples of basic science discoveries making ...

Stigma as a barrier to mental health care

2014-09-05

Over 60 million Americans are thought to experience mental illness in a given year, and the impacts of mental illness are undoubtedly felt by millions more in the form of family members, friends, and coworkers. Despite the availability of effective evidence-based treatment, about 40% of individuals with serious mental illness do not receive care and many who begin an intervention fail to complete it. A new report, published in Psychological Science in the Public Interest, a journal of the Association for Psychological Science, investigates stigma as a significant barrier ...

An 'anchor' that keeps proteins together

2014-09-05

All organisms react to different external and internal stimuli: if, for example, the hyphae fungus Sordaria macrospora is supplied with food, it produces fruiting bodies as part of its oestrous cycle. To initiate this reaction, signals have to be transmitted within the cell, which are conveyed by proteins. Physical proximity is a fundamental requirement for different proteins to be able to communicate with each other. Generating that proximity is what scaffolding proteins do, by binding like an anchor to several proteins and keeping them together for the duration of signal ...

Use of dengue vaccine may cause short-term spikes in its prevalence

2014-09-05

CORVALLIS, Ore. – As researchers continue to work toward vaccines for serious tropical diseases such as dengue fever, experts caution in a new report that such vaccines will probably cause temporary but significant spikes in the disease in the years after they are first used. This counter-intuitive and unwanted result could lead to frustrated policy makers, a skeptical public and concerns that the vaccine is making things worse instead of better, researchers say. In fact, it will just be the natural result of complex interactions between less-than-perfect vaccine protection ...

E-cigarettes: Studies presented at the ERS Congress

2014-09-05

Munich, Germany: The latest evidence on the potential benefits and risks of e-cigarettes has been presented this week at the European Respiratory Society's International Congress in Munich. Electronic cigarettes have received much attention in recent years as their use has increased across Europe. As the devices are relatively new, there is little long-term evidence detailing the potential harm or benefit that these devices can cause. During the ERS Congress, a number of abstracts will be presented on the topic. The key outcomes are revealed here: Research into ...

IBD patients: Consider giving infliximab a second try

2014-09-05

Bethesda, MD (Sept. 5, 2014) — Restarting infliximab therapy after a drug holiday is safe and effective for patients with inflammatory bowel disease (IBD), according to a new study1 in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological Association. "Our findings suggest that starting infliximab after a history of prior therapy can be very beneficial to patients," said lead study author Filip Baert, MD, PhD, from the department of gastroenterology, University Hospitals Leuven in Belgium. "Most striking, ...

New blood test could offer more tailored treatment of ovarian cancer

2014-09-05

A new blood test allowing doctors to predict which ovarian cancer patients will respond to particular types of treatment is a step closer following a new study by Manchester scientists. Researchers from The University of Manchester and The Christie NHS Foundation Trust - both part of Manchester Cancer Research Centre - say the test could be developed and used in hospitals within the next few years. It would mean medics could see which patients could benefit from blood vessel-targeting drugs - such as bevacizumab - in addition to conventional therapy. Meanwhilehile others ...

California blue whales rebound from whaling, first of their kin to do so

2014-09-05

The number of California blue whales has rebounded to near historical levels, according to new research by the University of Washington, and while the number of blue whales struck by ships is likely above allowable U.S. limits, such strikes do not immediately threaten that recovery. This is the only population of blue whales known to have recovered from whaling – blue whales as a species having been hunted nearly to extinction. Blue whales – nearly 100 feet in length and weighing 190 tons as adults – are the largest animals on earth. And they are the heaviest ever, weighing ...

Glanville fritillary genome sequenced at the University of Helsinki

2014-09-05

The Glanville fritillary has long been an internationally known model species for ecology and evolutionary biology, whose population biology has been studied on the Åland Islands for more than twenty years. Now the species has become even more significant. Led by Research Professor Ilkka Hanski, the Metapopulation Research Group (MRG) at the University of Helsinki has sequenced the full genome of the Glanville fritillary together with three groups from the Institute of Biotechnology at the same university. Before the sequencing of the Glanville fritillary genome, which ...

Near-extinct African amphibians 'invisible' under climate change

2014-09-05

An international team of researchers has found that the majority of threatened species are 'invisible' when using modern methods to predict species distributions under climate change. Using African amphibians as a case study, the researchers found that more than 90 per cent of the species listed as threatened on The IUCN Red List of Threatened Species are omitted by the most popular tools for species distribution modelling. The study, led by researchers from the Universities of York and Copenhagen and the United Nations Environment Programme World Conservation Monitoring ...

LAST 30 PRESS RELEASES:

How rice plants tell head from toe during early growth

Scientists design solar-responsive biochar that accelerates environmental cleanup

Construction of a localized immune niche via supramolecular hydrogel vaccine to elicit durable and enhanced immunity against infectious diseases

Deep learning-based discovery of tetrahydrocarbazoles as broad-spectrum antitumor agents and click-activated strategy for targeted cancer therapy

DHL-11, a novel prieurianin-type limonoid isolated from Munronia henryi, targeting IMPDH2 to inhibit triple-negative breast cancer

Discovery of SARS-CoV-2 PLpro inhibitors and RIPK1 inhibitors with synergistic antiviral efficacy in a mouse COVID-19 model

Neg-entropy is the true drug target for chronic diseases

Oxygen-boosted dual-section microneedle patch for enhanced drug penetration and improved photodynamic and anti-inflammatory therapy in psoriasis

Around the world, children’s cooperative behaviors and norms converge toward community-specific norms in middle childhood, Boston College researchers report