The skin is the human body's most vulnerable organ, defending against insult, injury, and infection. It communicates the unseen workings of the inner body, signaling through changes in color and texture when other systems are functioning or faltering. It is the most visible organ, exposed to the elements, to light, to toxins, and to the unrelenting gaze of ourselves and others. And yet, despite its visibility, it maintains its secrets. Perhaps nowhere is this more obvious than in the ongoing struggle to understand the pathogenesis of atopic dermatitis, particularly the role of the epidermal barrier.

It turns out, new research suggests, the epidermal barrier is just half the story. Experts had speculated about a role for tight junctions (TJs) in the pathogenesis of atopic dermatitis, and evidence for their contributions now exists. Writing in The Journal of Allergy and Clinical Immunology (e-pub, December), investigators have shown decreased expression of the tight junction proteins claudin-1 and claudin-23 in patients with AD, but not in those with psoriasis or in normal controls. Furthermore, silencing claudin-1 expression in human keratinocytes diminished tight junction function and enhanced keratinocyte proliferation. These are intriguing findings for a disease that affects millions of individuals and, despite recent significant advancements, remains a therapeutic challenge.

The current age of barrier-focused therapy is the result of more than a decade of research into the structure and function of the epidermal barrier and has opened the door to new approaches in the management of this and other inflammatory skin diseases. Could in-depth study of tight junctions yield additional therapeutic opportunities?

No one knows what additional secrets the skin may reveal in coming years, but we now know that mastering the epidermal barrier is just scratching the surface. More therapeutic developments are sure to lie ahead for patients who suffer with dermatologic diseases—as well as the skin specialists who treat them— and we look forward to exploring them and their clinical relevance in the pages of Practical Dermatology.