New research has found that skin flora is associated with lupus

In people with lupus erythematosus, the immune system works against
the body.
The disease mainly affects adolescents and women in their 20s, who begin to experience symptoms
such as fever, kidney failure, hair loss, epilepsy, and joint pain.
70% of people with lupus have systemic lupus erythematosus (SLE), which affects the whole body, including organs and skin, and can be fatal
if left untreated.

Some people may be more likely to get lupus due to genetic reasons, but what ultimately triggers the disease is unknown
.
A new study published today (Oct.
28) in Science Immunology offers a possible answer by finding that skin microbes can induce full-blown systemic lupus
in mice.

Gut microbes may also play a role in disease progression, and some studies suggest that antibiotics can relieve systemic lupus erythematosus symptoms in
mice.

Co-author Hitoshi Terui, a dermatologist at Northeastern University School of Medicine, said many studies have shown a link between gut microbes and autoimmune diseases, but none have linked skin microbes to autoimmune inflammation, although researchers have suspected that the epidermis — specifically the skin cells that produce keratin-producing — are linked
to lupus.

Terui and his colleagues used a mouse model of Sjögren syndrome, a milder autoimmune disease that is also present in about 20 percent of human SLE patients
.
The mice lacked a functional protein called IκBζ, which helps fight infection, but is only found in the
skin.
These mice produced autoantibodies similar to those in humans with Sjögren syndrome, as well as some autoantibodies associated with lupus, and had another symptom
of dermatitis, lupus.

The researchers first observed that the skin swabs of IκBζ knockout mice contained more Staphylococcus aureus than normal mice
.
qPCR revealed one possible reason: Compared to wild-type mice, skin cells of IκBζ knockout mice produced less mRNA needed to make antimicrobial peptides (AMP), which are key small molecules
in the fight against infection.
Mice treated with oral antibiotics for Staphylococcus aureus showed less severe autoimmune symptoms
.
The antibiotics also lowered their autoantibody levels, improving their dermatitis, suggesting that Staphylococcus aureus may be linked to
the disease.

The team then applied more Staphylococcus aureus to the skin of the knockout mice and found that their levels of autoantibodies, such as anti-double-stranded DNA and anti-Smith antibodies (both highly specific for lupus patients) increased relative to control mice
.
"It was the most exciting time," Terui said
.
Compared to wild-type controls, the bacterium exacerbated inflammation and worsened autoimmune symptoms
in knockout mice.
Knockout mice also developed kidney failure, a common complication
of SLE.

The study also linked
two cytokines, IL-17 and IL-23, to worsening of autoimmune symptoms.
Histological experiments showed that knockout mice had higher levels of T cells than normal mice, and these cells produced IL-17
.
Not only is IL-17 present in the epidermis, but the researchers also found higher levels of cytokine circulation
in knockout mice.
Finally, the researchers found that the use of antibodies that block IL-17 and IL-23 alleviated SLE symptoms in knockout mice exposed to the bacteria, suggesting cytokine activity
in SLE progression.

According to Terui, the findings aren't entirely surprising
.
Scientists have been "very familiar with the IL-17/IL-23 pathway because it is used to treat .
.
.
Another autoimmune disease psoriasis"
.

Further culture experiments showed that keratinocytes were involved in inducing autoimmune inflammation
.
The keratinocytes of knockout mice undergo apoptosis when co-cultured with Staphylococcus aureus, which causes neutrophils to produce histone-rich reticular structures called neutrophil extracellular traps
.
These structures can trap and kill pathogens, and can also induce T cells to produce IL-17
by activating dendritic cells.

Kahlenberg cautions: "They tease out this mechanism in this paper and do a very good job, but I think how it translates to the effects of Staphylococcus aureus and human lupus is still a question
that needs to be studied.
" Several studies have shown that IL-17 signaling plays an important role
in (lupus) mouse models.
But when we looked at human data, especially in the skin, we didn't see IL-17 at work
.
”

The researchers also caution that dysfunctional IκBζ is not yet directly linked to human lupus, and that more research
is needed before these findings can be translated.
They noted that patients with atopic dermatitis, a disease in which Staphylococcus aureus is found in skin lesions, are at increased
risk of systemic lupus erythematosus.
Still, Terui and study co-author Kenshi Yamasaki, a dermatologist at Tohoku University in Japan, said they hope clinical trials using therapies with anti-IL-17 and anti-IL-23 antibodies could ease symptoms
in SLE patients.
"I believe this mechanism applies to humans as well," Yamasaki said
.