A defect in a deeper layer of the skin known as the "tight junctions" may play a key role in the development of atopic dermatitis.
Standard thinking has until recently held that a defect in the stratum corneum is responsible for making patients vulnerable to atopic dermatitis/eczema, new study results show that a defect in a deeper layer of the skin known as the “tight junctions” may also play a key role in the development of this common dermatological condition.
According to a news release from the University of Rochester Medical Center, researchers there think 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.”
Lisa Beck, MD, associate professor in the Department of Dermatology, Anna De Benedetto, MD, postdoctoral-fellow at the Medical Center, and colleagues used resistance and permeability tests to discover that tight junctions “were strong and tight in healthy skin samples, yet loose and porous in the skin of eczema patients.”
They discovered that a specific tight junction protein known as claudin-1 “is significantly reduced in the skin of eczema patients, but not in healthy individuals or individuals with psoriasis.” They also showed that “reducing claudin-1 expression in skin cells from healthy donors made the tight junctions leaky and more permeable.”
De Benedetto said that “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… 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.”
Based on these results, the University of Rochester has applied for patent protection for increasing claudin-1 with drug compounds to treat eczema. The study, titled “Tight Junction Defects in Patients with Atopic Dermatitis,” was published on the website of the Journal of Allergy and Clinical Immunology.
According to Beck, “Over the past five years, disruption of the skin barrier has become a central hypothesis to explain the development of eczema… 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.” The next step is 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,” Beck said.
According to the University of Rochester news release, Beck and her team plan to build on these findings “by investigating the immunologic consequences of tight junction disruption in the skin and whether there is a relationship between barrier disruption and subjects’ intractable itch” and gene mapping claudin-1 to try to identify mutations in patients with eczema.