U. ROCHESTER (US) — Two faulty barriers—not one as previously thought—are influential in how eczema develops, allowing microscopic intruders to wreak havoc on the skin’s immune system.
While the stratum corneum, the skin’s upper-most layer, has been pinned as the culprit in previous research, a new study published in the Journal of Allergy and Clinical Immunology finds that a second skin barrier structure, consisting of cell-to-cell connections known as tight junctions, is also faulty in eczema patients and likely plays a role in the development of the disease.
Tightening both leaky barriers may be an effective treatment strategy for eczema patients, who often have limited options to temper the disease.
“Over the past five years, disruption of the skin barrier has become a central hypothesis to explain the development of eczema,” says Lisa Beck, associate professor of dermatology at the University of Rochester.
“Our findings challenge the belief that the top layer of the skin or stratum corneum is the sole barrier structure: It suggests that both the stratum corneum and tight junctions need to be defective to jumpstart the disease.”
There are no treatments that target skin barrier dysfunction in eczema, which allows pollen, mold, pet dander, and dust mites to be sensed by the skin and causes dry, red, itchy skin.
To treat it, physicians typically prescribe anti-inflammatory drugs, like prednisone, and a variety of topical anti-inflammatory creams and ointments, but they are associated with modest benefit, negative side effects, and cost concerns.
“We want to figure out what current eczema therapies do to both barrier structures and start thinking about new treatments to close the breaks that let irritants in and water out and subsequently drive the inflammation and dryness that is characteristic of the disease,” notes Beck.
To better understand the role of tight junctions in eczema, researchers studied skin samples from eczema patients and healthy individuals. Using resistance and permeability tests, they discovered that tight junctions, which act like a gate controlling the passage of water and particles, were strong and tight in healthy skin samples, yet loose and porous in the skin of eczema patients.
On further investigation, they found that a particular tight junction protein, claudin-1, which determines the strength and permeability of tight junctions in skin, is significantly reduced in the skin of eczema patients, but not in healthy individuals or individuals with psoriasis, another common chronic skin disease.
Researchers demonstrated that reducing claudin-1 expression in skin cells from healthy donors made the tight junctions leaky and more permeable, a finding in line with results of other research groups.
“Since claudin-1 was only reduced in eczema patients, and not the other controls, it may prove to be a new susceptibility gene in this disease,” says Anna De Benedetto, postdoctoral-fellow and first author of the new study.
“Our hypothesis is that reduced claudin-1 may enhance the reactivity to environmental antigens and lead to greater allergen sensitization and susceptibility in people with eczema.” If the team’s hypothesis stands up in future research, increasing claudin-1 to combat eczema could be a new treatment approach worth exploring.
Barrier problems, and in particular tight junction defects, are recognized as a common feature in many other inflammatory diseases, such as inflammatory bowel disease and asthma, where the lining of the intestine and the airways is weakened, which is why Beck decided to focus on the role of this barrier structure in eczema.
Eczema affects up to 17 percent of children and about six percent of adults in the United States – close to 15 million Americans. While there are varying severities of eczema, all have an itch that can make it difficult to focus on daily activities and to sleep.
Scientists from Johns Hopkins University, National Jewish Health, the University of California, San Diego, Children’s Hospital Boston, Oregon Health & Science University, the University of Bonn (Germany), and Technische Universität München (Germany), contributed to the research.
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