NEW YORK, NY – July 12, 2012. When the Beatles sang “Here Comes the Sun” in the 1960’s, few thought about the dangers of its ultraviolet (UV) rays. But in the decades since, scientists have shown us the damage caused by sunburn, when the skin becomes red, painful and inflamed. New findings based on a novel research discovery first funded by the Lupus Research Institute (LRI) now offers a possible explanation on how sunlight triggers inflammation, which may lead to better treatments for autoimmune diseases such as lupus.
Just published in Nature Medicine, the study shows that a sunburn is caused by the immune system’s protective response to damage caused by the sun’s UV radiation to the RNAs (ribonucleic acids) in skin cells. RNAs are molecules related to DNA that carry the message when genes are turned on, help maintain cell function, and determine the fate of cells. These study findings potentially open the way to blocking the inflammatory process, the scientists said, and have implications for a range of medical conditions and treatments.
"It was well known that UV light can damage DNA, but it hadn't been suspected that it damages RNA, or that the RNA damage was the signal that led to inflammation," notes senior study author Professor Richard Gallo, from the University of California, San Diego. “Our discovery suggests a way to get the beneficial effects of UV therapy without actually exposing our patients to the harmful UV light. Also, some people have excess sensitivity to UV light, patients with lupus, for example. We are exploring if we can help them by blocking the pathway we discovered."
Building on Earlier LRI-Funded Discovery
This work is building on findings among lupus patients first discovered by co-authors Dr. Eric L. Greidinger, Miami Veterans Affairs Medical Center and Division of Rheumatology, University of Miami Miller School of Medicine and his colleague Laisel Martinez, MS, Miami Veterans Affairs Medical Center. Dr. Greidinger and Ms. Martinez developed biological components and provided specialist knowledge critical to the success of the later study.
"Our expertise with the specific-type of RNA and understanding of how the immune system triggers inflammation were developed in the course of work first funded by the LRI and subsequently by NIH and the Veterans' Association," said Greidinger. "The striking sensitivity of skin cells to RNA modified by UV-light provides a new possible explanation for skin rashes experienced by lupus patients following sun-exposure."
Dr. Greidinger is continuing work in this area with funding leveraged by the initial LRI grant.
Current LRI-Funded Innovative Research Furthering Understanding of the Sun’s Impact
Dr. Gallo’s paper explains how sunlight triggers inflammation in healthy skin and may provide clues as to why skin inflammation happens so readily in lupus patients in response to UV light. Two current LRI-funded studies are exploring new ideas on why the skin of lupus patients reacts so readily to sunlight.
Funded by a 2012 LRI grant, Sandra Wolin, MD, PhD at Yale University is studying a form of lupus of the skin to explore how lupus autoantibodies combine with particular types of RNA to trigger skin rashes.
With a 2011 LRI grant, Theresa T. Lu, MD, PhD at New York’s Hospital for Special Surgery, is zeroing in on the initial blood vessel activation that permits inflammatory cells from the bloodstream to enter the skin. She hypothesizes that people with lupus have larger numbers of immune system “guard” or “sentinel” cells in their skin that can activate blood vessels. This innovative hypothesis would explain why the blood vessels in the skin are so readily activated, causing the skin to become inflamed —and why exposure to ultraviolet light from the sun only worsens the situation.
Each of the three studies has the potential to bring us closer to understanding skin inflammation in lupus.