Eczema symptoms include an itchy rash accompanied by dry and cracked skin. Doctors treat skin inflammation with topical steroids, or in more severe cases, administer immunosuppressants, similar to those used to treat other autoimmune diseases. But currently there is no cure for the condition, and many sufferers rely on home treatments such as wraps, moisturizers or herbal remedies.
Although its root cause is unknown, eczema is linked to hyper-reactivity of immune cells called mast cells following exposure to allergens and irritants, similar to asthma and food allergies. For a decade, LJI’s Toshiaki Kawakami, M.D., PhD., has defined mast cell signaling that either worsens or ameliorates eczema, relying heavily on animal models of atopic dermatitis that he established. His most recent work, studying human skin tissues, confirms that these mouse models mimic the allergic immune response seen in humans.
One of Kawakami’s critical discoveries was that a protein that controls gene expression, called STAT5, drives up the number of mast cells in skin of some eczema sufferers. Accordingly, mice that he genetically engineered to lack Stat5 in mast cells became resistant to atopic dermatitis, confirming that Stat5 is a major player in disease pathogenesis. His lab has also reported that a different signaling factor called phospholipase C-beta3 (PLC-β3) antagonizes mast cell activation by blocking STAT5. These discoveries suggest that eczema severity could be modulated either by muffling STAT5 or boosting PLC-β3 activity.
LJI investigator Michael Croft, Ph.D., takes a complementary approach to treating eczema by blocking a protein called LIGHT, which belongs to the TNF family of pro-inflammatory cytokines. They initially reported that blocking LIGHT activity reduced thickening and scarring of tissue in asthmatic lung. Croft’s more recent work hints that anti-LIGHT drugs could also relieve symptoms of scleroderma, chronic obstructive pulmonary disease (COPD), and eczema. These findings are particularly relevant to treatment of patients resistant to steroid treatment.