'Gatekeeper' identified for skin inflammation

Toronto - A new study has identified key signals that regulate protective and sometimes pathological skin inflammation, and also identifies a “gatekeeper” that, when lost, can cause inflammatory skin disease in the absence of injury or infection.

Medical News Today reports that the findings could lead to new treatment strategies for people who suffer from inflammatory skin diseases.

A research team led by Rama Khokha, Ph.D., of the Ontario Cancer Institute, Toronto, conducted the study to determine how skin cells regulate the function of immune cells. Medical News Today quotes Dr. Khokha as saying, “We knew that skin cells called keratinocytes direct the local immune response, yet the signaling networks in the skin that control the immune response were poorly defined. In our study we investigated whether an enzyme called ADAM17 is involved in ‘crosstalk’ between the skin and the immune system. ADAM17 sheds proteins from the cell surface and has been implicated in immune cell function and development.”

Researchers inactivated the gene for ADAM17 in the skin of adult mice and observed spontaneous production of inflammatory proteins by keratinocytes, which resulted in skin inflammation and immune cell proliferation. Investigators then went on to show that ADAM17 controls Notch signaling in the epidermis, noting that the Notch signaling pathway has been linked to the maintenance of normal skin and the prevention of inflammatory skin disease. Researchers found that the reactivation of Notch rescued local skin inflammation and abnormal immune cell proliferation in the mice lacking the gene for ADAM17.

Medical News Today quotes Dr. Khokha as saying, “Our study provides the first demonstration of the physiological requirement of ADAM17 in Notch signaling and demonstrates that loss of this gatekeeper triggers an immune response, even in the absence of injury or infection. A better understanding of the mechanisms that regulate communication between immune and non-immune cells will be of significant value in the treatment of diseases affecting the skin and other barrier tissues.”

The study was published by Cell Press online in the journal Immunity.

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