December 2019

The skin

The skin is the largest organ of the body. It is made up of cells arranged in layers and acts as a barrier to the outside world. In dry skin, this barrier is compromised. Many of us experience occasional dry skin (e.g. during winter months or after too much showering), but for some, it is a debilitating sign of a chronic skin condition. So, what is dry skin and why are some people more prone than others? Below we have letter extracts from two important cells in the epidermis. By hearing more about their normal functions, we can begin to appreciate why their dysfunction may contribute to dry skin.

Epidermis

Epidermis = the surface layer of the skin (above the dermis). Can be split up into sublayers including: Stratum Corneum – outer layer of ‘dead’ corneocytes Stratum Granluosum – living, granular skin cells (keratinocytes) Stratum Spinosum & Stratum Basale – deeper layers of skin cells and immune cells Skin cells migrate from deeper to outer layers and thus eventually become corneocytes.

Stratum Granulosum

Letter from a Keratinocyte

I have to take a lot of the credit. I live in the Stratum Granulosum and without the tight junctions that exist between my cells, no one would have the right fluid to live in¹. You see, the well-travelled corneocytes above like one climate whilst the cells below, just starting their journey, like another. I am responsible for stopping the fluids mixing and for secreting the lipids into the upper Stratum Corneum layer to maintain the oily environment the corneocytes love so much. I’m the delivery guy, providing the ceramides and cholesterol to minimise water loss through the skin. I suppose that the corneocytes are the bricks of the skin barrier and I provide the mortar! One day, when I’m further along in my journey towards the upper layers of the skin, it will be my turn to be a brick. When that day comes, I hope that the keratinocytes that have taken my place do as-good-a job as I have in providing the mortar.

Lipids = fatty/oily molecules that are soluble in water Ceramides = a particular family of waxy lipid molecules

We have known about ceramides since early studies in the 1990’s when scientists showed that there was a reduction ceramide levels in those suffering with atopic dermatitis or “eczema” – a condition that is classically associated with a dry skin². Ceramides were also depleted in the skin of older people which agrees with the observation that skin becomes drier as you get older and suggests that a low ceramide level isn’t specific to eczema. This still leaves us with chicken and egg scenario – does ceramide deficiency cause dry skin or does the dry skin lead to loss of ceramides?

Whilst we are yet to fully answer this question, scientists have investigated whether replacing ceramides will improve dry skin. In a small study on patients with controlled eczema³, a moisturiser containing a ceramide precursor was applied to one leg only and dryness compared after 28 days. There was significantly less water loss from the skin in the treated leg which is a promising result. Nevertheless, further studies are required to confirm that it is the ceramides specifically that are making the difference.

Not everyone with dry skin has low ceramides so what else could go wrong? Let’s hear from the predecessor of the keratinocyte and see what she has to say for herself.

Stratum Corneum

Letter from a Corneocyte

You heard from one of my dear delivery guys earlier. They do play an essential role and I used to be smug like them too. Now that I’m further along in my journey and a resident of the Stratum Corneum, I have a different perspective. Yes, I am shrunken and arguably less active, but I am now much tougher. Think of me as a guard, protecting the cells below from drying out. As I went through the maturation journey, my precious granules released pro-filaggrin that was broken up into filaggrin⁴.The filaggrin pulled at my keratin skeleton and flattened me out! In the last stages of my journey, my filaggrin will be broken down further into something called natural moisturising factor which is important for keeping skin hydrated⁵.

Maturation journey = The slow process in which active keratinocytes migrate from deeper layers of the skin (stratum granulosum) and become tough corneocytes in the outer layer (stratum corneum). The resulting corneocytes are sometimes considered dead but this is misleading as they still have plenty of essential functions, only some of which are discussed here. Filaggrin = (filament aggregating protein) a protein that binds to keratin fibres in skin cells and causes the keratin skeleton of the cell to condense as the cell  migrates. It is stored as a larger pro-filaggrin in the granules of the skin cell.

The corneocyte has every reason to brag as she plays a multitude of roles in keeping our skin supple. Dry skin may arise when this maturation process doesn’t happen efficiently. Having a shorter pro-filaggrin gene (FLG), for example, means that it is broken up into fewer filaggrin molecules and this increases risk of dry skin conditions, as shown in genetic studies^6,7. Thus, your FLG gene may predispose you to the dry skin associated with eczema and other drier skin conditions like ichthyosis vulgaris.

Understanding this association can be improved by studying mice. The flaky tale (ft) mouse has a mutation in its FLG gene and, as you might have guessed, it has dry, flaky skin on its tale that mimics eczema⁸. Interestingly, the ft mice also had a more severe allergic sensitisation to dust mite than normal mice. This links dry skin and a more porous skin barrier to allergy, a common phenomenon and a topic for future posts!

Letters from our skin cells help us understand our skin

In conclusion, the letters from cells in the epidermis have helped us to understand why our skin can get dry in some conditions. The studies into these conditions are ongoing and new discoveries may help scientists design treatments that tackle the underlying causes of dry skin. If you’re interested in getting into the nitty gritty science, have a look at some of the studies referred to in this article. Likewise, the British Skin Foundation funds a number of important research projects and your support is welcomed.  

Shannon Guild, University of Oxford Biomedical Sciences

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Bibliography

1. Kubo, A., Nagao, K. & Amagai, M. Review series Epidermal barrier dysfunction aKubo, A., Nagao, K., & Amagai, M. (2012). Review series Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases, 122(2). doi:10.1172/JCI57416DS1nd cutaneous sensitization in atopic diseases. 122, 440–447 (2012).
2. Imokawa, G. et al. Decreased Level of Ceramides in Stratum Corneum of Atopic Dermatitis: An Etiologic Factor in Atopic Dry Skin? J. Invest. Dermatol. 96, 523–526 (1991).
3. Simpson, E., Böhling, A., Bielfeldt, S., Bosc, C. & Kerrouche, N. Improvement of skin barrier function in atopic dermatitis patients with a new moisturizer containing a ceramide precursor. J. Dermatolog. Treat. 24, 122–125 (2013).
4. Sandilands, A., Sutherland, C., Irvine, A. D. & McLean, W. H. I. Filaggrin in the frontline: role in skin barrier function and disease. J. Cell Sci. 122, 1285–1294 (2009).
5. Denecker, G., Ovaere, P., Vandenabeele, P. & Declercq, W. Caspase-14 reveals its secrets. J. Cell Biol. 180, 451–458 (2008).
6. Ginger, R. S., Blachford, S., Rowland, J., Rowson, M. & Harding, C. R. Filaggrin repeat number polymorphism is associated with a dry skin phenotype. Arch. Dermatol. Res. 297, 235–241 (2005).
7. Brown, S. J. et al. Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose-dependent effect. J. Invest. Dermatol. 132, 98–104 (2012).
8. Moniaga, C. S. et al. Flaky tail mouse denotes human atopic dermatitis in the steady state and by topical application with Dermatophagoides pteronyssinus extract. Am. J. Pathol. 176, 2385–2393 (2010).