The mechanism of atopic dermatitis has been studied
Atopic dermatitis (atopic eczema) is a chronic inflammatory skin disease, which is essentially an allergic reaction. Researchers from the La Jolla Institute (USA) have described an important factor that plays a key role in skin inflammation.
It was found that the LIGHT protein, one of the factors of tumor necrosis, directly controls the proliferation of keratinocytes, as well as the expression of periostin, a protein that causes clinical manifestations of atopic dermatitis and other inflammatory skin diseases, for example, scleroderma.
Periostin is used in the clinic as a marker of allergic diseases, for example, bronchial asthma and atopic dermatitis. The fact that LIGHT protein controls its production makes it an attractive target for new drugs against atopic dermatitis and other inflammatory skin diseases.
The drug, which is an antibody to the LIGHT protein, successfully fought the manifestations of the disease. This means that LIGHT blocking therapy can significantly ease the course of atopic dermatitis.
Left: periostin (pink) is produced in large quantities in atopic dermatitis. On the right: the result of the introduction of antibodies to the LIGHT protein – the secretion of periostin decreased significantly.
LIGHT is a cytokine produced by T-lymphocytes. It performs its functions through two receptors: HVEM and LTßR. Previous studies have shown that LIGHT plays a key role in skin inflammation in scleroderma, an autoimmune disease accompanied by excessive collagen production and manifested by thickening and scarring of the skin.
In order to find out whether the LIGHT protein is involved in skin inflammation in atopic dermatitis, the researchers conducted a series of experiments on mouse models. In mice that were "turned off" LIGHT synthesis, atopic dermatitis proceeded without pronounced manifestations. The same was demonstrated in models whose skin keratinocytes lacked the HVEM receptor. This is an important observation, as it proved that it is enough to block the synthesis of just one receptor to facilitate the course of atopic dermatitis.
In-depth analysis showed that the LIGHT protein stimulates the proliferation of keratinocytes, causing the restructuring of skin tissue. In addition, it induces excessive periostin production. The mechanism of action of periostin has not yet been studied, but it is already known that it plays an important role in the process of skin inflammation in scleroderma and atopic dermatitis.
Thus, the LIGHT protein directly leads to fibrosis – a structural restructuring of the skin, manifested in its thickening and compaction.
The researchers tested an experimental drug, which is an antibody to the LIGHT protein, which blocked its binding to the HVEM receptor of keratinocytes of the skin. The drug was administered to mice in the advanced stage of atopic dermatitis. As a result, there was a decrease in inflammatory manifestations, the thickening of the skin stopped.
This proves that therapy based on blocking the LIGHT protein can significantly alleviate the condition of patients with atopic dermatitis and even reverse the course of the disease.
Article by Rana Herro et al. LIGHT–HVEM signaling in keratinocytes controls development of dermatitis is published in the Journal of Experimental Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of La Jolla Institute: LJI researchers discover key driver of atopic dermatitis.