Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march

Some things are so evident that we take them for granted.  Take our skin for example.  We live in our skin and, for the most part, don’t give a second thought about it.  But skin is more than meets the eye.  It is vital for immunity, not only because it protects us from the outside but also because it fine tunes how our immune system responds to the various stimuli it encounters.  For those who have atopic dermatitis, a type of allergic disease that affects the skin leading it to become dry, irritated, and thickened, we see one result of a poor skin function.  In this month’s issue of JACI, Egawa and Kabashima discuss the role of skin barrier dysfunction in atopic dermatitis (J Allergy Clin Immunol 2016; 138(2): 350-358).

To understand the skin, we have to think about it in layers.  The topmost layer, called the stratum corneum, is a little like a wall, with flattened cells called corneocytes working like bricks and intercellular lipids functioning as mortar.  Together, they maintain the integrity of the skin.  But in atopic dermatitis, the wall is weakened.  Mutations in filaggrin, a protein important in making the corneocytes, have been associated with an increased risk of developing atopic dermatitis.

With the growing knowledge of genetics and immunology, there are beginning to be great insights into how atopic dermatitis starts to take hold.  In addition to filaggrin mutations, there’s a host of newer mutations that lead to the irritation, peeling, and thickening of the skin.  Mutations in genes encoding some proteins, like LEKTI and KLKs, have to do with the way that skin desquamates, or sheds, whereas others, like CLDN1, influence the tight junctions that maintain the integrity of the skin barrier.  And, in addition to these structural proteins, the immunologic messengers, particularly type 2 cytokines like IL-4, IL-13, IL-31, and IL-33, are found to be key in the development of atopic dermatitis.

As Egawa and Kabashima note, the skin is a very complex organ, and one that we are just starting to understand from an immunologic perspective.  Its importance cannot be overstated, not only because it brings us closer to figuring out what causes diseases like atopic dermatitis, but also because it opens the door towards finding new, effective medications and therapies that can target proteins like filaggrin.  In turn, this can improve the lives of the millions who live with atopic dermatitis, and the diseases that are associated with it.