Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps Research Institute Scientists Discover Important Wound-Healing Process

27.09.2013
Scientists at The Scripps Research Institute (TSRI) have discovered an important process by which special immune cells in the skin help heal wounds.

They found that these skin-resident immune cells function as “first responders” to skin injuries in part by producing the molecule known as interleukin-17A (IL-17A), which wards off infection and promotes wound healing.

“This appears to be a critical and unique component of mammals’ defense against skin wounds, and we hope that it will point the way towards better therapies for people with difficulties in healing wounds,” said TSRI Professor Wendy L. Havran.

Havran was senior author of the study, which was published this week online ahead of print by the Journal of Clinical Investigation.

More than Sentinels

Havran and other researchers have shown in recent years that special immune cells known as dendritic epidermal T cells (DETCs) are the only resident T cell population in the outer layer of skin (epidermis) of mice—and are resident in human skin, too. These cells are now thought to serve as the immune system’s principal sentinels in the skin—when they detect damage signals from nearby wounded skin cells, they summon other, non-skin-resident immune cells to the site of the wound. Skin injuries in mice that have been bred to lack DETCs take much longer than normal to heal.

In the new study, Havran’s laboratory looked for new ways in which DETCs contribute to wound healing.

In one set of experiments, Senior Research Associate Amanda S. MacLeod, the lead author of the study, and other members of the team tried to determine whether DETCs in mice produce IL-17A in response to skin wounding. IL-17A had been considered mainly a recruiter of other immune cells and thus a promoter of inflammation in most places in the body. Havran and her colleagues had found evidence that it appears in and around skin wounds in mice soon after an injury occurs.

The scientists soon determined that mice that lack IL-17A activity healed wounds on their skin much more slowly than normal—very much like mice that lack DETCs. Applying IL-17A to the skin of such mice repaired their wound-healing defects. The team then showed that the rise in local IL-17A levels after a skin wound depended critically on the activation of skin-resident DETCs—pointing to these DETCs as the likely source of the immune signaling molecule. In the mice that lack IL-17A, adding normal DETCs from other mice fully restored a healthy wound-healing capacity and did so only when the added DETCs contained the gene that allows these cells to produce IL-17A.

The scientists found that DETCs are indeed the primary producers of IL-17A after skin injuries, but she observed that some and not all DETCs perform this function. “Only a subset produces IL-17A upon skin injury, although the surface markers on these cells seem identical to those of other DETCs,” MacLeod said. “Why only some DETCs respond to wounds in this way is something we plan to explore further.”

In a last series of tests, the scientists observed that DETCs started pumping out IL-17A as soon as they detected damage signals from nearby skin cells, called keratinocytes. The surge in IL-17A levels didn’t merely summon other immune cells into the skin. Even before those other immune cells arrived on the scene and inflammation set in, the IL-17A induced local keratinocytes to start making special proteins that are known to combat bacteria, viruses and other microbes—and are also known to promote the crucial skin regrowth and remodeling that are needed to heal a wound.

“This ‘cross-talk’ between skin-resident T cells and nearby keratinocytes is critical for re-establishing the skin barrier following wounding,” MacLeod said.

Next Steps

One of the next steps, Havran noted, will be to investigate whether a similar process occurs in human skin following wounds. “We’ve previously shown that skin-resident T cells normally contribute to wound healing in people, and that those same T cells are defective in some patients with chronic wounds,” she said. “Chronic wounds are an increasing clinical problem, particularly in the elderly, the disabled and people with diabetes, and so we hope that our results, particularly the wound-healing role of IL-17A, will help lead to better ways of treating such conditions.”

She notes, too, that IL-17A is often considered chiefly a pro-inflammatory factor, which some anti-inflammatory therapies are designed to suppress. “IL-17 inhibitors are now used in the treatment of the skin condition called psoriasis, which raises the possibility that those patients might become more susceptible to the development of chronic wounds,” she said.

Havran, MacLeod and their colleagues also hope to learn further details of the molecular cross-talk between DETCs and keratinocytes, as well as the role of DETCs in protecting against other environmental threats, such as the ultraviolet radiation that causes sunburn and skin cancers. “We suspect that these skin-resident T cells also help protect keratinocytes from ultraviolet-induced DNA damage,” MacLeod said.

Other contributors to the study, “Dendritic epidermal T cells regulate skin antimicrobial barrier function,” were Saskia Hemmers, Olivia Garijo, Marianne Chabod, Kerri Mowen and Deborah A. Witherden, all of TSRI. For more information on the paper, see http://www.jci.org/articles/view/70064

The study was funded in part by the National Institutes of Health (R01AI036964, R01AI067460 , R01A1099728 and 5T32AI007244), Deutsche Dermatologische Gesellschaft and Arbeitskreis Dermatologische Forschung.

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. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now 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.
For information:
Office of Communications
Tel: 858-784-2666
Fax: 858-784-8136
press@scripps.edu

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Health and Medicine:

nachricht Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>