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DERMAL
THE ROLE OF KERATINOCYTES IN ATOPIC DERMATITIS/ECZEMA
Part One By Gay Wardle
Daily, the human body is being attacked by countless invaders. Bacteria, fungi, viruses, parasites, chemical, allergens, pollutants, the list is long. Remarkably the body manages all of these by physically blocking their entry inside and they are held off by the skin`s defense. This defense system is due to the function of the keratinocyte cells which forms a barrier creating the first line of defense which protects the body against these invaders. Unfortunately, there are times when this defense system is weak or weakened by either external factors or internal factors, allowing a portal of entry of any of these invaders which can cause harm and disease. Knowing that the keratinocyte is the major cell that forms the epidermis, it is therefore essential that we understand the role of keratinocytes and their relationship to the development of atopic dermatitis/eczema.
Roles in epidermal structure:
The keratinocyte is a major player in the structure of the epidermis, in fact it is 90% of the epidermis. Desmogleins and desmocollins are the intercellular proteins that are produced by the keratinocyte cell and then there are intracellular proteins, such as plakoglobin, desmoplakins, and intermediate filaments. These form the intercellular structures that we know as desmosomes which act as the bonds that hold the epidermis together. It just takes one of these intercellular structures to be weakened by either external factors such as bacteria or internal factors and the coherence of the epidermis is lost. Then we have a dysfunctional keratinocyte where they separate. The next stage from this is the formation of an intra-epidermal blister formation and a break down in the epidermis.
Roles in barrier proteins:
Keratinocyte cells produce proteins such as filaggrin, involucrin and loricrin that are proteins dominant in creating the physical barrier of the corneum layer. There are many papers and studies showing that filaggrin gene mutations have been found in patients with atopic dermatitis and eczema as well as ichthyosis. These findings have been linked to allergen polysensitivity which supports the fact where there is a defect of filaggrin there will be an easy portal of entry for allergen that will trigger allergic reaction. The bacteria Staphylococcus aureus has a higher incidence of colonization in people with atopic dermatitis/eczema. Filaggrin gene expression in keratinocytes is vital to the skin barrier, without it we lose the protein filaggrin. Add to this loss of keratinocyte cell adhesion, migration and proliferation, the end result would not only be disruption to the barrier layer but to the cell cycle as well. Tight junctions are another structure that I want 30
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to mention. These are the intercellular junctions that form the assembly between adjacent keratinocytes in the stratum granulosum layer (keratinocytes create the formation of these tight junction proteins). Claudin-1 is a protein that has been identified throughout the five layers of the epidermis and is a primary protein in tight junctions. If this protein is not present in tight junctions the risk of fast trans-epidermal water lost is very high, the skin becomes dry and cracked. When we look at how the skin responds to wound healing, tight junctions and Claudin-1 proteins are a key component, without them the skin would not heal. There is a high reduction of claudin-1 protein and filaggrins found in people that have atopic dermatitis/eczema. References have been made that absence of claudin-1 proteins and filaggrins increases inflammation.
Epidermal-dermal Junction:
We have talked about the importance of the keratinocyte cell and its role in providing proteins and structure that are essential for the integrity of the epidermis. They are also hugely responsible for the proteins that are needed for adherence between the epidermis and the dermis, known as the epidermal-dermal junction. The role is accomplished through the keratinocyte’s synthesis of several important skin basement membrane anchoring proteins, which are vital connecting components for this epidermal-dermal junction. It has been studied that in genetic skin diseases and autoimmune diseases that these basement membrane structures are non-functional. If the basement membranes are weakened either by genetic defect or by assault from autoantibodies in auto-immune diseases, all the skin`s integrity is compromised. The outcome will be separation to the epidermis and the dermis. There will be subepidermal blister formation and a very weak barrier layer.
Immune regulation:
Keratinocytes are communicators with both lymphocytes and Langerhans cells. Lymphocytes are immune cells and are part of the adaptive immune system, they are responsible for immune memory and the effector cells for defense against previously recognized pathogens. It is interesting to note that there almost twice as many lymphocytes present in the skin than there are circulating. Hence the importance of
the keratinocytes and lymphocyte relationship. Langerhans cells are antigen-presenting cells, and they are responsible for immune recognition and immune activation. Add to this they are also responsible for maintaining skin homeostasis by activating the skin`s T cells. Skin-localised anti-microbial substances are produced by keratinocytes, which are is an immediate defense against invading microorganism. This is done by the ability to mount an innate immune response. When there is an injury or infection, keratinocytes produce many anti-microbial peptides which are important for the innate immune defense function. The peptides maintain a homeostasis with commensal micro-organisms in a symbiosis manner. There function is to defend against invading bacteria, viruses, fungi, and some parasites. They can also activate surrounding cells, such as keratinocytes and immune cells to regulate many functions including angiogenesis, epithelialization, and immunity. Other roles of these peptides are also implicated in allergic disease including atopic dermatitis/eczema. With atopic dermatitis people some of these peptides are not induced and this allows the start of infection. The keratinocyte is the principal cell in the epidermis and is responsible for generating and maintaining the integrity of the epidermis. Besides being the structural foundation of the epidermis, keratinocytes also possess functions capable of interacting with their environment immunologically. My journey on the topic of dermatitis will continue in part two in the next journal. A career dedicated to sharing her passion for lifelong learning, Gay Wardle has established herself as one of the beauty industry’s most respected icons. Her roles as an educator, business owner, mentor, coach, and skin expert has seen her feature as keynote speaker at industry symposiums on a global scale. Committed to the personal and professional development of the beauty & aesthetic industry at large, Gay is synonymous with supporting business owners become the very best versions of themselves. www.gaywardle.com education@gaywardle.com
