Keratinocyte

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Keratinocyte is the predominant cell type in the epidermis, the outermost layer of the skin, constituting 95% of the cells found there.[1] Those keratinocytes found in the basal layer (Stratum germinativum) of the skin are sometimes referred to as "basal cells" or "basal keratinocytes".[2]

Contents

Function

The primary function of keratinocytes is the formation of a barrier against environmental damage such as pathogens (bacteria, fungi, parasites, viruses), heat, UV radiation and water loss. Once pathogens start to invade the upper layers of the epidermis, keratinocytes can react with the production of proinflammatory mediators and in particular chemokines such as CXCL10, CCL2 which attract leukocytes to the site of pathogen invasion.[citation needed]

Structure

A number of structural proteins (filaggrin, keratin), enzymes (proteases), lipids and antimicrobial peptides (defensins) contribute to maintain the important barrier function of the skin. Keratinization is part of the physical barrier formation (cornification), in which the keratinocytes produce more and more keratin and eventually undergo programmed cell death. The fully cornified keratinocytes that form the outermost layer are constantly shed off and replaced by new cells.[citation needed]

Cell differentiation

Keratinocytes are formed first by differentiation from epidermal stem cells (transit amplifying cells), residing in the lower part of the stratum basale of the epidermis, attached to the basement membrane through hemidesmosomes.[3] Those stem cells and their differentiated progeny are organized into columns named epidermal proliferation units.[4][5] Keratinocytes in the stratum basale layer of the epidermis are attached together through desmosomes and will proliferate through a few rounds of cell divisions within the stratum basale before moving up through the epidermis as they differentiate.

During this differentiation process, keratinocytes permanently withdraw from the cell cycle, initiate expression of epidermal differentiation markers, and move suprabasally as they become part of the stratum spinosum, stratum granulosum and eventually become corneocytes in the stratum corneum.

Corneocytes are keratinocytes that have completed their differentiation program and have lost their nucleus and cytoplasmic organelles.[6] Corneocytes will eventually be shed off through desquamation as new one come in.

At each stage of differentiation, keratinocytes express specific keratins, such as keratin 1, keratin 5, keratin 10 and keratin 14, but also other markers such as involucrin, loricrin, transglutaminase, filaggrin and caspase 14.

In humans, it is estimated that keratinocytes turnover from stem cells to desquamation every 40–56 days[7] whereas in mice the estimated turnover time is 8–10 days.[8]

Factors promoting keratinocyte differentiation:

Since keratinocyte differentiation stops keratinocyte proliferation, factors that promote keratinocyte proliferation should be considered as preventing differentiation, such as:

Interaction with other cells

Within the epidermis keratinocytes are associated with other cell types such as melanocytes and Langerhans cells. Keratinocytes form tight junctions with the nerves of the skin and hold the Langerhans cells and intra-dermal lymphocytes in position within the epidermis. Keratinocytes also modulate the immune system: apart from the above mentioned antimicrobial peptides and chemokines they are also potent producers of anti-inflammatory mediators such as IL-10 and TGF-β. When activated, they can stimulate cutaneous inflammation and Langerhans cell activation via TNFα and IL-1β secretion.[citation needed]

Keratinocytes contribute to protecting the body from ultraviolet radiation (UVR) by taking up melanosomes, vesicles containing the endogenous photoprotectant melanin, from epidermal melanocytes. Each melanocyte in the epidermis has several dendrites that stretch out to connect it with many keratinocytes. The melanin is then stored in the keratinocytes' nuclei, where it protects the DNA from UVR-induced damage.[26]

Role in wound healing

Wounds to the skin will be repaired in part by the migration of keratinocytes to fill in the gap created by the wound. The first set of keratinocytes to participate in that repair come from the bulge region of the hair follicle and will only survive transiently. Within the healed epidermis they will be replaced by keratinocytes originating from the epidermis.[27][28]

At the opposite, epidermal keratinocytes, can contribute to de novo hair follicle formation during the healing of large wounds.[29]

Keratinocytes migrate with a rolling motion during the process of wound healing.[30][31]

Sunburn cells

A sunburn cell is a keratinocyte with a pyknotic nucleus and eosinophilic cytoplasm that appears after exposure to UVC or UVB radiation or UVA in the presence of psoralens. It shows premature and abnormal keratinization, and has been described as an example of apoptosis.[32][33]

See also

References

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