Filaggrinįilaggrin is a specialised structural ‘ filament-aggregating protein’ responsible for the structural and mechanical integrity of the stratum corneum. The acidic skin surface, together with an intact stratum corneum, prevents colonisation with pathogens, and supports the normal skin microbiome. The acid pH also restricts the activity of kallikrein (KLK)-5 and -7, which cleave the extracellular corneodesmosomal proteins important in corneocyte adhesion. Enzymes in the stratum corneum including β-glucocerebrosidase and acid sphingomyelinase, function optimally in an acidic environment, and are responsible for the production of ceramides and free fatty acids which affect diffusion through the epidermis. The human skin surface has a normal pH range of 4.5 to 5.5, and the acidity is important in the skin permeability barrier. Skin (bio)chemistry with barrier functions pH The subcutis also acts as a mechanical barrier by absorbing mechanical shocks applied to the skin (such as a punch), protecting deeper structures including bone. Adipose tissue is responsible for heat production and forms an insulating layer, thereby playing a critical role in thermoregulation. The subcutis is composed predominantly of fat cells ( adipocytes). Prevents the growth of certain bacteria.Dense hair can protect the epidermis from sun exposure.Is an early-warning detection system on the scalp to prevent minor skin trauma.Holds a layer of warm air against the skin to minimise heat loss.The cuticle between the proximal nail fold and the nail plate provides a waterproof barrier against chemical and microbial entry.The diffusion path length which is determined by the thickness of the stratum corneum, numbers of layers of corneocytes, their size, and their cohesion.The unique lamellar organisation of the lipid matrix and its interaction with protein components of keratinocytes, including tight junctions and scaffolding proteins.The rate of diffusion across the stratum corneum is influenced by: Diffusion through the epidermis can be via one of two routes: intracellular through the epidermal lipid matrix, or transcellular across the corneocytes. In our research we use cultured human skin and lipid model systems to study in detail the barrier function and the changes in this barrier induced by inflammation.A key barrier function of the epidermis is to control diffusion of molecules across the skin transepidermal water loss (TEWL) from inside to outside, and chemicals from the outside environment to inside. Most of the studies have been performed in atopic dermatitis skin as this is the most prevalent inflammatory skin disease: in Western countries around 25% of the young children are suffering from this disease. In this research we focus on changes in the barrier function of inflammatory skin diseases and how to repair this barrier by using formulations. Perturbations in the lipid composition and organisation will have a profound impact on the diffusion process as this will facilitate intercellular penetration and as such reduce the skin barrier. The crystalline nature and the presence of proper lamellar phases limit the diffusion of compounds travelling along this lipid matrix. The lipids assemble in crystalline lipid lamellae. The lipid matrix in the stratum corneum plays a crucial role in the skin barrier function. As modern antigens often lack a strong antigenicity, the antigens are combined with adjuvants and/or encapsulated in nanoparticles to enhance the immune response. In our studies we use microneedles and we mainly focus on vaccination. For this reason specialized drug delivery systems are developed. This makes the delivery of high molecular weight compounds, such as therapeutic proteins and antigens a challenge. The stratum corneum controls the flux of substances into and out of the body and protects the body from unwanted influences from the environment. The stratum corneum consists of enucleated dead cells (corneocytes) embedded in a lipid matrix. One of the key functions of the skin is its barrier function, which is located in the uppermost layer of the skin, the stratum corneum. The Skin Barrier and Vaccination group is led by Prof.
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