Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape

The barrier function of skin is indispensable for terrestrial animals. This function is mainly carried out by the epidermis, more specifically by its granular and cornified layers. The major structural components associated with this function are the intercellular lipid layer, desmosomes, corneodesmosomes, tight junctions, cornified cell envelope and keratin filaments. In this review, we discuss the current knowledge of their ultrastructure, their molecular basis and their relevance to skin disease.

Section: Tight Junctionsmentioning

confidence: 99%

Molecular basis of the skin barrier structures revealed by electron microscopy

Ishida‐Yamamoto

Igawa

Kishibe

2018

“…Immortalized human keratinocytes, HDK1 (human dermal keratinocyte 1), were obtained by transfecting TERT, a mutant form of CDK4 and cyclin D1 into normal human keratinocytes . We used cells at passage around 20 for 3D reconstructed epidermis.…”

Section: Methodsmentioning

confidence: 99%

“…Ipponjima et al observed fine morphological changes in chromosomes of epidermal basal cells in mice that were genetically modified to visualize the nuclei in 3D by two‐photon laser scanning microscopy . 3D live imaging by Yokouchi et al captured dynamic changes in the honeycomb pattern of tight junctions in the granular layer of mice that were genetically modified to detect tight junctions . However, these 3D live imaging techniques used for mice cannot be directly applied to live human tissues.…”

Section: Introductionmentioning

confidence: 99%

Development of 3D imaging technique of reconstructed human epidermis with immortalized human epidermal cell line

Inoue

Hasegawa

Miyachi³

et al. 2018

The epidermis, the outermost layer of the skin, retains moisture and functions as a physical barrier against the external environment. Epidermal cells are continuously replaced by turnover, and thus to understand in detail the dynamic cellular events in the epidermis, techniques to observe live tissues in 3D are required. Here, we established a live 3D imaging technique for epidermis models. We first obtained immortalized human epidermal cell lines which have a normal differentiation capacity and fluorescence-labelled cytoplasm or nuclei. The reconstituted 3D epidermis was prepared with these lines. Using this culture system, we were able to observe the structure of the reconstituted epidermis live in 3D, which was similar to an in vivo epidermis, and evaluate the effect of a skin irritant. This technique may be useful for dermatological science and drug development.

“…The granular layer, which is traditionally defined by its appearance on haematoxylin and eosin‐stained skin sections, is the site of the terminal cellular remodelling during differentiation and the site at which tight junctions form between neighbouring cells. Tight junctions create a grid within the granular layer and establish the effective paracellular diffusion barrier of the epidermis . Here, we refer to the layer of epidermal cells that are connected by functional tight junctions as “tight junction layer.” It is dynamic and allows the outward passage of differentiating but still viable cells.…”

Section: The Skin Barrier Depends On Continuous Renewal and Executionmentioning

confidence: 99%

Control of cell death‐associated danger signals during cornification prevents autoinflammation of the skin

Eckhart

Tschachler

2018

The function of the skin as a barrier to the environment is mainly achieved by the outermost layers of the epidermis. In the granular layer, epidermal keratinocytes undergo the last steps of their terminal differentiation program resulting in cornification. The coordinated conversion of living keratinocytes into corneocytes, the building blocks of the cornified layer, represents a unique form of programmed cell death. Recent studies have identified numerous genes that are specifically expressed in terminally differentiated keratinocytes and, surprisingly, this genetic program does not only include mediators of cornification but also suppressors of pyroptosis, another mode of programmed cell death. Pyroptosis is activated by inflammasomes, leads to the release of interleukin-1 (IL-1) family cytokines, and thereby activates inflammation. In addition, inhibitors of potentially pro-inflammatory proteases and enzymes removing danger-associated cytoplasmic DNA are expressed in differentiated keratinocytes. We propose the concept of cornification as an inherently hazardous process in which damaging side effects are actively suppressed by protective mechanisms. In support of this hypothesis, loss-of-function mutations in epidermal protease inhibitors and IL-1 family antagonists suffice to induce autoinflammation. Similarly, exogenous disturbances of either cornification or its accompanying control mechanisms may be starting points for skin inflammation. Further studies into the relationship between cornification, pyroptosis and other forms of cell death will help to define the initiation phase of inflammatory skin diseases and offer new targets for disease prevention and therapy.