The HSS study revealed how ultraviolet light triggers immune activation and disease outbreaks in lupus patients

After sun exposure, patients with systemic lupus erythematosus (SLE) often develop a rash, which is often accompanied by an outbreak
of systemic disease.
The link between ultraviolet (UV) light and lupus disease flares is well known, but how UV exposure actually triggers disease is poorly
understood.

In a new study presented at the ACR Proceedings of the American College of Rheumatology 2022 Annual Meeting, researchers from the Hospital for Special Surgery (HSS) report that they have discovered a potential mechanism explaining this association: reduced lymphatic drainage, which contributes to the creation of photosensitivity and immune responses
in lymph nodes.
Studies have also shown that promoting lymphatic drainage may be an effective treatment
for lupus photosensitivity and autoimmunity.

"When there is a systemic outbreak of disease in lupus patients, it affects any organ of their disease," said senior author Theresa T.
Lu, M.
D.
, who serves as the St.
Giles Research Chair at the HSS Institute, is a faculty member of HSS Pediatric Rheumatology and Rheumatology, and is a professor
of microbiology, immunology and pediatrics at Weill Cornell Medical School.
"We wanted to see why skin exposure to sunlight affects internal organs
such as kidneys, heart and lungs.
"

Lead author William Ambler, MD
, added: "This study reveals how sun exposure and ultraviolet light can lead to more autoantibodies in the blood of lupus erythematosus patients.
" William Ambler, M.
D.
, is a former investigator at HSS in Dr.
Lu's lab and is now a Metzger Scholar
in Translational Medicine at the National Institute of Arthritis, Musculoskeletal and Dermatology at the National Institutes of Health.

The skin communicates with the immune system by sending cellular and molecular signals through lymphatic vessels to the lymph nodes where the immune response began
.
The signals sent by the skin to the lymph nodes control the type of
immune response.
Lymphatic vessels also play a role
in removing fluid and cells from the skin.
If the lymphatic vessels are not working properly, bringing skin signals to the lymph nodes, the resolution of skin inflammation is delayed, causing false signals to be sent to the lymph nodes
.

Research by Lu's lab has shown that in lupus erythematosus patients, lymph flow from the skin to the draining lymph nodes is reduced
.
The researchers hypothesized that this reduction in flow altered the immune response of the lymph nodes, making them more pathogenic
.
They decided to take a closer look at this communication and how it affects immune function
.
The current study used SLE patient samples and mouse models
.

The researchers studied skin biopsies
of lupus patients and healthy volunteers who served as controls.
When they looked at samples from lupus patients, they found that these lymphatic vessels were more dilated
compared to healthy controls.
This provides evidence of
poor lymphatic flow in patients with lupus erythematosus.

They then studied a mouse model of SLE, injected into the skin using a dye to visualize the flow
of lymphatic fluid.
They found that when lupus mice were exposed to ultraviolet radiation, more dye remained on the
skin.
This proves that the lymphatic vessels are not clearing fluid
as they should.

Importantly, the researchers then looked to see if they could improve some of the disease characteristics
of the mice by using manual lymphatic drainage techniques to control the flow of lymph.
This therapy is used in patients with certain types of cancer, especially breast cancer, to prevent lymphedema (fluid accumulation and swelling)
after surgical removal of lymph nodes.
They found that lymphatic drainage in mice reduced the number of plasma cytoplasms and germinal center B cells, two types of cells that play an important role
in lupus.

The researchers note that the study is also important because it promotes a broader understanding
of how the skin and organs communicate through lymph nodes and the immune system.