Lymphatic Dysfunction Found to Play Big Role in SLE Photosensitivity

Poor drainage in lymphatic system might explain processes leading to lupus flares

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by Lindsey Shapiro |

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Reduced lymphatic drainage might explain why skin reactions to sunlight, or photosensitivity, may lead to systemic immune reactions and overall disease flareups in people with systemic lupus erythematosis (SLE), a study suggests.

Data showed that the flow of the skin’s lymphatic fluid — which sends cells and molecular signals to the lymph nodes, where immune responses are regulated — was lower than normal in both SLE patients and mouse models.

Dysfunction of the lymphatic system with retention of lymphatic fluid in tissues may aggravate inflammation and delay resolution of inflammatory and immune reactions.

However, promoting lymphatic fluid drainage in the mouse models was found to reduce skin photosensitivity and systemic immune reactions — supporting the potential benefit of therapeutically targeting the lymphatic system in patients living with lupus.

The findings were discussed in a presentation, titled “Lymphatic Dysfunction and Immune Activation in Lupus,” at the American College of Rheumatology’s annual meeting, ACR Convergence 2022, held Nov. 10–14 in Philadelphia.

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Lupus can lead to photosensitivity, skin lesions, and systemic flares

SLE patients commonly experience sensitivity to ultraviolet (UV) light, such as that coming from sunlight. Not only does this photosensitivity cause skin lesions on sun-exposed areas, but people diagnosed with SLE may also experience systemic lupus flares that affect their internal organs.

“When people with lupus have a systemic flare of their disease, it can affect any organ that is part of their disease,” Theresa T. Lu, MD, PhD, the study’s senior author and the St. Giles chair for research in the Hospital for Special Surgery (HSS) Research Institute, said in a HSS press release.

“We wanted to look at why sun exposure at the level of the skin affects internal organs like the kidneys, heart and lungs,” added Lu, who is also a faculty member in pediatric rheumatology and rheumatology at HSS, and a professor of microbiology and immunology, and pediatrics at Weill Cornell Medicine, both in New York.

Similar to the circulatory system, the lymphatic system circulates fluid throughout the body via a network of vessels. But instead of blood, it slowly circulates lymphatic fluid, a collection of the extra fluid that drains from cells and tissues.

our results demonstrate that lupus skin is characterized in part by lymphatic dysfunction, and that this dysfunction contributes to both [skin] photosensitivity and draining lymph node B cell responses

The lymphatic system works as a communication route between tissues and the immune system, with the drained lymphatic fluid from body tissues, including the skin, being filtered at immune-cell-filled structures called lymph nodes.

There, the fluid is cleared of potential threats such as microbes and waste products, and then returned to blood circulation. If harmful molecules are in the fluid, they activate immune cells in the lymph nodes and send them in the blood to the site of invasion.

The proper flow of communication between the skin and the lymph nodes is critical for ensuring proper immune function. Dysfunction of the lymphatic system can lead to inappropriate immune responses in the lymph nodes that delay resolution of inflammation and autoimmunity.

Motivated by the hypothesis that the lymphatic system may be impaired in SLE, Lu’s team and colleagues examined the lymphatic system in skin biopsies from SLE patients and healthy people. They found that the lymphatic vessels were dilated, or widened, in patients more than normal, consistent with poor drainage of lymph fluid from the skin.

Moreover, experiments showed that lymphatic flow was reduced after exposure to UV light in two mouse models of lupus compared with healthy mice. In these mice, the lymph fluid was retained in the skin rather than being properly drained out.

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Manual drainage of lymphatic fluid reduces skin photosensitivity in mouse model

When the researchers manually drained the lymphatic fluid in one of the mouse models, skin photosensitivity was reduced, evidenced by reduced ear swelling and less infiltration of immune cells.

Of note, this drainage technique is used in people with certain types of cancer to prevent the accumulation of lymph fluid after their lymph nodes have been surgically removed.

Moreover, the intervention reduced immune B-cell responses in the lymph nodes. These antibody-producing cells are known drivers of autoimmunity in SLE and other inflammatory diseases.

Overall, the findings offer insights into a potential mechanism by which light exposure might cause both skin and systemic immune responses in SLE.

“Together, our results demonstrate that lupus skin is characterized in part by lymphatic dysfunction, and that this dysfunction contributes to both [skin] photosensitivity and draining lymph node B cell responses,” the researchers wrote, adding that the study “points to lymphatic function as a therapeutic target.”

Still, clinical trials are needed to evaluate the safety and effectiveness of manual lymphatic drainage in SLE patients, the team noted.