Researchers Discover Key Driver of Atopic Dermatitis

Source: La Jolla Institute for Allergy and Immunology

Summary: Researchers in their latest study, reveal an important player that promotes skin inflammation in atopic dermatitis and the characteristic thickening of the skin.

Atopic dermatitis is also known as atopic eczema, is a chronic pruritic inflammatory skin condition that is driven by an allergic reaction. It results in itchy, red, swollen, and cracked skin. Researchers from the La Jolla Institute for Allergy and Immunology in their latest study, reveal that LIGHT (protein) – a member of the tumor necrosis factor (TNF) superfamily, directly controls the hyperproliferation of keratinocytes as well as the expression of periostin, a protein that contributes to the clinical features of atopic dermatitis as well as other inflammatory skin diseases such as scleroderma. LIGHT is a cytokine primarily produced by T cells and exerts its function through two receptors, HVEM and LTβR. The fact that LIGHT acts upstream of periostin, it can potentially be a good clinical target for treatment of atopic dermatitis and other inflammatory skin diseases. The study findings were published in the Journal of Experimental Medicine.

Atopic Eczema

Periostin (shown in pink) is being used in the clinic as a marker for allergic diseases such as asthma as well as atopic dermatitis. Left image: Periostin is overexpressed in atopic dermatitis. Right image: Blocking LIGHT also blocks periostin expression. Credit: Dr. Rana Herro, La Jolla Institute for Allergy and Immunology

Researchers used an experimental model for atopic dermatitis that replicates the human disease to find out whether LIGHT contributes to skin inflammation in atopic dermatitis. Their experiments revealed that LIGHT-deficient mice only displayed minimal clinical symptoms compared to normal control mice. The same was true for animals that only lacked the LIGHT-receptor HVEM in keratinocytes, the predominant cell type in the outermost layer of the skin. A closer look revealed that LIGHT stimulates the proliferation of keratinocytes and also induces the expression of periostin. The research team used an existing therapeutic antibody to block the interaction of LIGHT with its receptor, HVEM after the disease had already manifested. The antibody treatment suppressed inflammation and strongly reduced epidermal thickening.

Lead author, Dr. Rana Herro said, “That’s great news for patients suffering from eczema”, “Our findings suggest that therapies that block LIGHT signaling might halt atopic dermatitis in humans and maybe even reverse disease symptoms.”

More Information: Rana Herro et al, “LIGHT–HVEM signaling in keratinocytes controls development of dermatitis”, The Journal of Experimental Medicine (2018). DOI: 10.1084/jem.20170536

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