Stylised image of Urushiol (in green), the 'active ingredient' in poison ivy, entrapped by CD1a molecule (in pink), which mediates the inflammatory response. Photo courtesy of Monash University
Researchers have identified the molecular connections between the sensitizing agents in poison ivy and immune response in the skin, potentially opening the window to researching ways to block this pathway to inflammation both from irritants and in inflammatory skin diseases.
In the study, published online in Nature Immunology (Aug. 22, 2016), transgenic mice were exposed to urushiol, a contact irritant found in poison ivy. The mice had been engineered to express the lipid-presenting molecule CD1a, which is abundantly expressed in human Langerhans cells but is not found in normal mice.
The exposure triggered CD1a-dependent skin inflammation that was driven by CD4+ helper cells producing the cytokines interleukin (IL)-17 and IL-22. This was similar to the cytokine signature seen in humans with poison ivy dermatitis follwing CD1a-mediated recognition of urushiol.
“For over 35 years we have known CD1a is abundant in the skin,” said study author Dr Jérôme Le Nours in a press release. “Its role in inflammatory skin disorders has been difficult to investigate and until now has been really unclear. Our work, which included imaging the CD1a–urushiol connection, represents clear evidence that CD1a is instrumental in skin-related diseases.”
Dr. Le Nours is a Biochemistry and Molecular Biology research fellow in the Faculty of Medicine, Nursing and Health Sciences at Monash University in Melbourne, Australia.
In vivo and clinical studies conducted at Harvard Medical School in Boston also showed that blocking the function of CD1a prevented the triggering of the skin-based allergic reaction in both a mouse model and in human patients with psoriasis.
“Future research could lead to the development of new treatments to combat minor skin irritations as well as chronic inflammatory skin diseases like psoriasis, eczema and rosacea,” study author Tang Yongqing, PhD, from the Department of Biochemistry and Molecular Biology at Monash University, said in the release.
“We now have a target to further investigate. Our basic discovery may make a big difference in the future treatment and prevention of inflammatory skin diseases,” Dr. Le Nours said.