The skin barrier: getting the right balance

The skin is a protective covering which isolates and protects our body, while still allowing it to relate with the outside world.

The epidermis, the outermost layer of the skin, acts as the front line of the body’s defences, and this is why we speak of the “epidermal barrier”.

To describe this barrier, the scientific world often compares it to a wall of tough bricks (corneocytes) which are held together by lipid cement (epidermal lipids).
The slightest change to this “wall” sets off an alarm and our body’s defences react by activating sophisticated protective mechanisms in the skin, enabling us to live in environments which would otherwise be inhospitable to us.

The barrier and its interactions

If we look closely at the epidermis, we discover it is surprisingly simple yet complex. So calling it a “covering made of dead cells”, a definition which was popular for a very long time, falls short of the mark, just as a “wall” made of bricks and cement, the commonly used definition nowadays, is rather reductive.

The structure of the epidermis and its barrier function are due to the continuous interaction between cells and other elements. This interaction allows our skin to relate with the outside world and instantly establish the best possible balance between the needs of the internal environment (homeostasis) and the external environment (1-4).

The layers of the epidermis: the three musketeers

A recently published article (5) used the metaphor of the three musketeers to describe the synergy between the elements of the skin barrier.

The skin barrier function has three main elements:

1) the STRATUM CORNEUM (SC) - the first level external barrier (air-water)

2) TIGHT JUNCTIONS (TJs) - protein structures which make up the second level internal barrier (liquid-liquid)

3) the LANGERHANS CELL NETWORK (LCs) – the skin’s immunological barrier

By working together, the three “musketeers” build a “barrier system” which constitutes effective skin surface surveillance. Let’s see how.

The stratum corneum

The stratum corneum, the outermost layer of the epidermis, limits the amount of water our body loses to the environment. Thanks to enzymes, it also creates optimal conditions (acidic pH) for the skin’s bacterial flora (microbiome) and helps the flora fight infections by synthesizing specific molecules (antimicrobial peptides).

The second level barrier

The second level barrier (TJs), located below the stratum corneum, consists of a group of proteins able to seal neighbouring cells when necessary to stop external agents penetrating, as it has been shown that these agents can cause inflammation and stimulate the immune system.

The immunological barrier

The immunological barrier (LCs), located below the second level barrier, is made of up immune cells which are activated by danger signals (cytokines, interleukins etc.) which the keratinocytes on the surface send when they detect damage in the external barrier (SC).

Every time damage is detected, the skin structure allows the immune cells to reach the more superficial layers with their extensions (dendrites) to identify the foreign elements, recognise them and eliminate them if they reappear.

From the epidermis to the rest of the body

We have seen that the epidermal barrier is a highly organised system whose elements work “one for all and all for one”, just like Dumas’s musketeers, thanks to a sophisticated internal communication network which ensures their continuous interaction.

Conditions which compromise the barrier function of the epidermis, like atopic dermatitis, can be damaging to our health if not treated properly and consistently as soon as they appear.

This damage is not restricted to the skin but can involve our organs and internal systems (the march of atopic eczema). Alterations in the epidermal barrier are an open door to allergies or the onset of respiratory conditions like asthma which can be serious and disabling (6).


The above information is not medical advice. It is given purely as an indication and is not intended as a substitute for professional advice.


  1. M. Elias Structure and function of the stratum corneum Extracellular matrix Journal of Investigative Dermatology 132 (2012) , 2131-2133
  2. R. Feingold, P. Elias Role of lipids in the formation and maintenance of the cutaneous permeability barrier Biochimica et Biophysica Acta 1841 (2014) 280-294
  3. Van Smeden , M.Janssen, G.S. Gooris, J.A. Bouwstra The important role of stratum corneum lipids for cutaneous barrier function Biochimica et Biophysica Acta 1841 (2014) 295-313
  4. Elias Lipid abnormalities and lipid-based repair strategies in atopic dermatitis Biochimica et Biophysica Acta 1841 (2014) 323-330
  5. Kubo, K. Nagao, M.Armagai Epidermal barrier dysfunction and cutaneous sensitization in atopic deseases The Journal of Clinical Investigation 122 (2012) 2, 440-447
  6. R. Smith, G. Knaysi, J.M.Wilson, J.A. Wisniewsld The skin as a route of allergen exposure: Part I Immune components and mechanisms Curr Allergy Asmtha Resp 17 (2017) 6 1-11