Exposure to UV light causes damage to everyone’s cellular DNA. Once the cells are damaged, the immune system clears them. However, people with lupus have a much slower clearance of these cells. The dead cells stick around in the body, triggering an immune system attack.
Previous studies have reported that in up to 80% of lupus patients, sun exposure can trigger both local skin inflammation and systemic flares, including kidney disease. However, little is known about the underlying mechanisms that drive this process. Now, researchers at the Geisel School of Medicine at Dartmouth and the University of Washington (UW) demonstrate that neutrophils not only infiltrate the UV-light exposed skin, but they also migrate to the kidney.
Their findings are published in the journal Proceedings of the National Academy of Sciences (PNAS) in a paper titled, “Acute skin exposure to ultraviolet light triggers neutrophil-mediated kidney inflammation.”
“Neutrophils are the most abundant leukocytes in circulation and the first responders to infectious and sterile inflammation, including skin exposure to ultraviolet (UV) light,” the researchers wrote. “We demonstrate that neutrophils not only migrate to the UV light–exposed skin but also disseminate systemically.”
The researchers decided to investigate the role of neutrophils, a type of white blood cell that responds to inflammation, that has been linked to skin and kidney tissue injury in lupus patients. In the study, they looked for markers of inflammation and injury in the skin, the blood, and the kidney at different time points following UV light exposure in mice.
“Interestingly, one subset of these neutrophils, the ones that we think are more damaging, first went to the skin that was exposed to the UV light and then turned around and went to the kidney,” explained Sladjana Skopelja-Gardner, PhD, an assistant professor of medicine at Geisel who worked with Keith Elkon, MD, at UW on the study. “That’s a bit unusual—we normally think of neutrophils as short-lived cells that sort of zoom to where the inflammation is and then die off there.”
The investigators found that a single exposure of skin to UV light stimulates inflammatory and injury processes in the kidney, including transient proteinuria, even in normal, healthy mice. Proteinuria is the presence of protein in the urine. It can often be a sign of kidney disease. Normally, protein should not be found in the urine. Transient proteinuria, the most common form, can be seen with stresses such as fever and exercise. Transient proteinuria is usually resolved on its own and does not require treatment.
“To be clear, normal, healthy mice don’t get the clinical type of kidney disease that you see in lupus patients,” added Skopelja-Gardner. “They get what we call subclinical injury, meaning there is an inflammatory and injury process happening in the kidney that is not visible by pathology or looking at the tissue itself. The mice recover and are fine afterwards.
“However,” she continued, “this subclinical injury may lead to pathologic consequences in the vulnerable setting of pre-existing inflammation in lupus patients, and lead to kidney disease flare after exposure to sunlight.”
The inflammatory and injury markers they discovered in the mouse kidneys following UV light exposure were very similar to the renal injury markers that are associated with more severe kidney damage in lupus patients.
These findings demonstrate that neutrophils mediate subclinical renal inflammation and injury following skin exposure to UV light.
“Overall, I think what our research demonstrates is that skin exposure to UV light can be the source of inflammatory pathways that are relevant to lupus, and that neutrophils play an important role as a pathogenic mediator in this process, contributing to kidney damage,” concluded Skopelja-Gardner.