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 Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>