Poison ivy and psoriasis: The treatment we’ve been itching for?

poison ivy psoriasis target CD1a
Poison ivy, psoriasis, eczema and other inflammatory skin conditions could have a shared targeted treatment. (Jessica Kim/Winau Lab)

The skin is a natural barrier against pathogens and harmful chemicals. But it isn’t bulletproof: contact allergens like poison ivy can trigger an immune response causing severe inflammation, itching and tissue damage. Mechanistically, what happens is that Langerhans cells — certain antigen-presenting cells in the immune system — initiate a chain reaction. This rallies helper T cells to the area, causing skin inflammation.

A protein called CD1a (Cluster of Differentiation 1a) has been thought to be part of this reaction. But until recently, its role was poorly understood, at least in part because there was no good test model. Research in Nature Immunology now suggests that targeting CD1a could lead to new therapies for poison ivy and other inflammatory skin conditions like psoriasis and eczema.

CD1a promotes skin inflammation in response to poison ivy

poison ivy psoriasis CD1aThe researchers, led by Florian Winau, MD, in the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, and investigators from Monash University and Kyoto University, began by looking at the chemical structure of the poison ivy antigen, urushiol. They noticed that it resembled compounds known to bind to CD1a.

To explore urushiol’s role in triggering the poison ivy reaction, the team used transgenic mice that express the human CD1a gene. Compared with wild-type mice, which lack CD1a, the transgenic mice had a strong inflammatory skin reaction to urushiol, resembling the rash and blisters people get when exposed to poison ivy.

Poison ivy dermatitis and psoriasis share a similar cytokine ‘signature’

The next step was to determine the immune response profile that urushiol triggers. Winau’s team found that both people and CD1a-transgenic mice with poison-ivy dermatitis mounted an immune response driven by CD4+ helper T cells that produce the cytokines IL-17 and IL-22 (TH17 cells).

We are currently developing CD1a-based drugs for the treatment of inflammatory skin disease. IL-17 and IL-22 are also known to contribute to psoriasis pathology. So the next logical step was to run tests in a psoriasis model, again using the CD1a-transgenic animals. Again the mice showed an enhanced inflammatory response, mirroring the helper T-cell response and cytokine-release profile seen in the poison ivy model.

What’s more, in both the poison ivy and psoriasis models, the inflammatory reaction improved when the CD1a transgenic mice were treated with antibodies targeting CD1a.

Targeting CD1a in inflammatory skin diseases

winau-cd1a-puff-of-smoke-jessica-kim-winau-labThe results held up when the researchers tested T cells from both healthy donors and patients with moderate-to-severe plaque psoriasis. They first exposed the cells to CD1a, by incubating them with antigen-presenting cells bearing the molecule. They then measured T-cell responses, and found that those from the psoriasis patients produced increased amounts of IL-17 and IL-22. As in the animal studies, this response disappeared when anti-CD1a antibodies were added to the dish.

Together, the mouse model and the human cell studies establish that CD1a controls both psoriatic skin inflammation and poison ivy dermatitis. Targeting CD1a could lead to novel, more effective treatments, Winau believes.

“Our studies using blocking antibodies reveal CD1a as a promising target for future therapies against skin inflammation,” he says. “We are currently developing CD1a-based drugs for the treatment of inflammatory skin disease. For many years, scientists speculated about the functions of CD1a, but in vivo evidence was lacking. We are excited about the translational potential of our studies to develop a first-in-class drug that blocks CD1a. ”

Read more about the research in the Harvard Gazette, Newsweek and on PCMM’s website.