Major shift in understanding how eczema develops
The cell-to-cell connections known as tight junctions plays a role in the development of the disease.
Washington: Our skin serves as a barrier protecting our body from hundreds of allergens, irritants, pollutants and microbes we come in contact with every day.
But in eczema patients, the skin barrier is leaky, allowing intruders to be sensed by the skin and subsequently wreak havoc on the immune system.
While the upper-most layer of the skin – the stratum corneum – has been pinned as the culprit in previous research, a new study has found that a second skin barrier structure, consisting of cell-to-cell connections known as tight junctions, is also at fault and 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,” said Lisa Beck, lead author and associate professor in the Department of Dermatology at the University of Rochester Medical Center.
“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,” she added.
Currently, there are no treatments that target skin barrier dysfunction in eczema. To treat eczema, physicians typically prescribe anti-inflammatory drugs, like prednisone, and a variety of topical anti-inflammatory creams and ointments.
But, modest benefit, negative side effects and cost concerns associated with these therapies leave patients and doctors eagerly awaiting new alternatives.
“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,” said Beck.
To better understand the role of tight junctions in eczema, Beck and her team 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.
They 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,” said first author Anna De Benedetto.
“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,” she added.
The study is published in the Journal of Allergy and Clinical Immunology.