Researchers have discovered a potential target for Tx of skin inflammation in eczema and psoriasis
Researchers from La Jolla Institute for Allergy and Immunology in San Diego, Calif. report that they may have discovered a common driver associated with skin inflammation in both psoriasis and atopic dermatitis.
The findings of their investigation were published online in the May 22, 2017 edition of Nature Communications. The data showed that TWEAK, a protein related to tumour necrosis factor (TNF), plays a major role in inducing pro-inflammatory signaling molecules that recruit immune cells to the skin.
“Atopic dermatitis and psoriasis are two distinct diseases that are induced by alternate immune responses and the factors involved are quite different,” said the lead investigator, Michael Croft, PhD. “Showing that TWEAK is a critical mediator in both conditions, makes it a potential therapeutic target for the treatment of inflammatory skin diseases in general.”
Dr. Croft is professor and head in the Division of Immune Regulation at La Jolla Institute for Allergy and Immunology.
“Atopic dermatitis and psoriasis are very common diseases and can have debilitating affects on people's daily lives,” says the study's first author Dr. Daniel Sidler, a primary investigator at the University of Bern in Switzerland. “Understanding the molecular basis of these diseases is crucial before we can seek new treatments for these and other inflammatory skin diseases.”
TWEAK alone is not associated with atopic dermatitis or psoriasis
In their current study, Dr. Croft and his team, in collaboration with researchers at the biotechnology company Biogen Idec in Cambridge, Mass, focused on TWEAK and its receptor, Fn14, which has previously been shown to participate in several inflammatory conditions such as inflammatory bowel disease, arthritis and lupus-like kidney disease.
“TWEAK and its signaling receptor, Fn14, have emerged as a fundamental molecular pathway regulating tissue responses after acute tissue injury and in many different contexts of chronic injury and disease,” said the co-senior author of the current study, Linda Burkly, PhD, senior distinguished investigator, and vice-president at Biogen Idec.
During the investigation, Dr. Sidler and colleagues found that when measuring TWEAK signalling in the skin, the expression of both the receptor and ligand was upregulated in both atopic dermatitis and psoriasis.
The findings revealed that keratinocytes and dermal fibroblasts responded to increased TWEAK activity by producing many chemoattractive and pro-inflammatory factors commonly found in atopic dermatitis and psoriasis. It also amplified disease-specific cytokines, namely IL-13 and IL-17, further explaining why it can contribute to two fundamentally different diseases.
“TWEAK alone doesn't cause atopic dermatitis or psoriasis, but triggers the production of chemokines that recruit pathogenic inflammatory cells to the skin regardless of the condition,” said Dr. Sidler. “Blocking TWEAK activity, alone or in combination with other treatments, may sufficiently control skin inflammation to clear up the debilitating symptoms and restore the quality of life [for people with] severe cases of [atopic dermatitis or psoriasis].”
Article source: La Jolla Institute for Allergy and Immunology