Atopic dermatitis and skincare
Skin barrier function
The epidermis is the outermost layer of the skin, and serves as a highly functional barrier that protects the inside of the body. It is itself comprised of four types of cells: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of those, keratinocytes make up more than 90% of epidermal cells, and play a critical role in preventing the infiltration of substances from the outside environment. The stratum corneum both physically and chemically blocks the penetration of microscopic material and ultraviolet rays, while the penetration of microbes is blocked by the secretion of natural immunity substances. It also prevents the evaporation of moisture from within the body, meaning that the skin has an advanced moisture-retaining function as well. It also maintains pH at a weakly acidic level to inhibit colonization of pathogenic bacteria. Before cells differentiate into the stratum corneum, they are known as granular cells. These cells play an important role in the formation of filaggrin proteins and supporting keratin protein adhesion. Filaggrin is broken down as it moves into the stratum corneum, functioning as natural moisturizing factor in the form of amino acids, urocanic acid, and so on. Note that keratinocytes exist as basal cells in the deepest layers of the epidermis, taking four to six weeks after they divide to differentiate while altering their gene expression. They then arrive in the outermost layers of the skin are naturally sloughed off. This entire process is known as epidermal turnover. During the differentiation process, keratinocytes create keratin filament in order to solidify their cytoskeletons. They also produce filaggrin, involucrin, loricrin, and serine-rich proteins that scavenge for active oxygen. All of these help enhance the skin’s barrier function 20.
There are also substances, primarily ceramide, that serve as sphingolipids between keratinocytes. In addition, cholesterol and fatty acids form a membrane with a lamellar structure that traps moisture and prevents it from evaporating. In atopic dermatitis, these outer layers have a mutation in the filaggrin genes that serve as this critical barrier or else some other problem that makes it impossible for the filaggrin proteins to function properly, which is believed to compromise the barrier. Furthermore, the amount of intercellular sphingolipid ceramide (which plays a critical role in both the barrier and moisture-retaining function of the stratum corneum) is reduced in patients with atopic dermatitis, creating a qualitative difference in their skin versus healthy people as well. This has led to the proposal that a reduction in ceramides is one trigger for atopic dermatitis 21. Because the skin is functioning poorly due to problems with both the quality and quantity of intercellular lipids, particularly ceramides, it has little ability to retain moisture, dries out, becomes itchy, and eventually cracks—worsening inflammation. This in turn is thought to boost Th2 immunity.
The epidermis also contains Langerhans cells. These cells are in charge of generating the immunological response to foreign bodies and infectious organisms. Langerhans cells that have engulfed foreign material digest it and trigger an immunological response in which they carry the waste material to the lymph nodes. Particularly when the barrier function has broken down in the epidermis, it has been reported that Langerhans cells respond by separating from the epidermis quickly (in just a few hours) after having engulfed the antigen and arrive at their designated lymph node eighteen hours later 22. This also triggers a Th2 response. Because IL-10 and IL-4 also express quickly when the barrier function breaks down, the Th2 response becomes the primary focus 23. The immunological response that Langerhans cells contribute to is thought to result in the high IgE levels seen in atopic dermatitis patients. The workings of the tight junction barrier function that exists in the granular layer of the epidermis (the one closely tied to Langerhans cells) are also thought to be critical 24.
Melanocytes produce melanin, distribute melanosomes (organelles that produce melanin) to the surrounding keratinocytes, and protect the nuclei of the keratinocytes from UV damage. Skin that has been exposed to ultraviolet light darkens due to melanin deposition, and this is thought to be a way for the cytokines (like stem cell factor and endothelin) and hormone peptides (likeα-melanocyte stimulating hormone) generated in the keratinocytes to work for the melanocytes in a paracrine way to promote the formation of melanin 25.
Finally, the α-MSH produced by the melanocytes not only activates melanin production, but in areas where there is skin inflammation, triggers T-reg cells to inhibit inflammatory response 26.
Dr. Masamitsu Ichihashi
Professor Emeritus, Kobe University
Dr. Ichihashi completed his doctoral program at the Kobe University Graduate School of Medicine. He specializes in dermatology, with a particular interest in researching how UV rays affect the skin over many years of exposure. He has also trained outside of Japan in dermatology and dermatological treatments.