Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells.
Function
The primary function of keratinocytes is the formation of a barrier against environmental damage by heat, UV radiation, dehydration, pathogenic bacteria, fungi, parasites, and viruses.
Pathogens invading the upper layers of the epidermis can cause keratinocytes to produce proinflammatory mediators, particularly such as CXCL10 and CCL2 (MCP-1) which attract , natural killer cells, , and to the site of pathogen invasion.
Structure
A number of structural proteins (
filaggrin,
keratin), enzymes (e.g.
), lipids, and antimicrobial peptides (
) 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 undergo terminal differentiation. The fully cornified keratinocytes that form the outermost layer are constantly shed off and replaced by new cells.
Cell differentiation
Epidermal stem cells reside in the lower part of the epidermis (stratum basale) and are attached to the basement membrane through
. Epidermal stem cells divide in a random manner yielding either more stem cells or transit amplifying cells.
Some of the transit amplifying cells continue to proliferate then commit to differentiate and migrate towards the surface of the epidermis. Those
stem cells and their differentiated progeny are organized into columns named epidermal proliferation units.
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 in the stratum corneum.
Corneocytes are keratinocytes that have completed their differentiation program and have lost their cell nucleus and organelles.
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 cell turnover from stem cells to desquamation every 40–56 days,
Factors promoting keratinocyte differentiation are:
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A calcium gradient, with the lowest concentration in the stratum basale and increasing concentrations until the outer stratum granulosum, where it reaches its maximum. Calcium concentration in the stratum corneum is very high in part because those relatively dry cells are not able to dissolve the ions.
-
Vitamin D3 (cholecalciferol) regulates keratinocyte proliferation and differentiation mostly by modulating calcium concentrations and regulating the expression of genes involved in keratinocyte differentiation.
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Cathepsin E.
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TALE homeodomain transcription factors.
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Hydrocortisone.
Since keratinocyte differentiation inhibits keratinocyte proliferation, factors that promote keratinocyte proliferation should be considered as preventing differentiation. These factors include:
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The transcription factor p63, which prevents epidermal stem cells from differentiating into keratinocytes.
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Vitamin A and its analogues.
-
Epidermal growth factor.
-
TGF alpha.
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Cholera toxin.
Interaction with other cells
Within the epidermis keratinocytes are associated with other cell types such as
melanocytes and
. Keratinocytes form
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.
Keratinocytes contribute to protecting the body from ultraviolet radiation (UVR) by taking up , vesicles containing the endogenous photoprotection melanin, from epidermal melanocytes. Each melanocyte in the epidermis has several that stretch out to connect it with many keratinocytes. The melanin is then stored within keratinocytes and melanocytes in the perinuclear area as supranuclear "caps", where it protects the DNA from UVR-induced damage.[
]
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.
At the opposite, epidermal keratinocytes, can contribute to de novo hair follicle formation during the healing of large wounds.
Functional keratinocytes are needed for tympanic perforation healing.[Y Shen, Y Guo, C Du, M Wilczynska, S Hellström, T Ny, Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations, PLOS ONE, 2012]
Sunburn cells
A sunburn cell is a keratinocyte with a
pyknotic cell nucleus and
eosinophilic cytoplasm that appears after exposure to
Ultraviolet C or
Ultraviolet B radiation or
Ultraviolet A in the presence of
. It shows premature and abnormal
keratinization, and has been described as an example of
apoptosis.
[
][
]
Aging
With age, tissue
homeostasis declines partly because
stem cell fail to self-renew or differentiate. DNA damage caused by exposure of stem/progenitor cells to reactive oxygen species (ROS) may play a key role in
epidermis aging. Mitochondrial superoxide dismutase (SOD2) ordinarily protects against ROS. Loss of SOD2 in mouse epidermal cells was observed to cause cellular
senescence that irreversibly arrested proliferation in a fraction of keratinocytes.
In older mice, SOD2 deficiency delayed
wound closure and reduced epidermal thickness.
Civatte body
A Civatte body (named after the French dermatologist
Achille Civatte, 1877–1956)
is a damaged basal keratinocyte that has undergone
apoptosis, and consist largely of keratin intermediate filaments, and are almost invariably covered with
, mainly IgM.
Civatte bodies are characteristically found in skin lesions of various
dermatosis, particularly
lichen planus and discoid lupus erythematosus.
They may also be found in graft-versus-host disease, adverse drug reactions, inflammatory
keratosis (such as lichenoid actinic keratosis and
lichen planus-like keratosis), erythema multiforme, bullous pemphigoid,
eczema, lichen planopilaris, febrile neutrophilic dermatosis, toxic epidermal necrolysis,
herpes simplex and
varicella zoster lesions, dermatitis herpetiformis, porphyria cutanea tarda,
sarcoidosis, subcorneal pustular dermatosis, transient acantholytic dermatosis and epidermolytic hyperkeratosis.
See also
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Epidermis
-
Skin
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Corneocyte
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Keratin
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HaCaT
-
List of human cell types derived from the germ layers
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Epidermidibacterium keratini
-
List of distinct cell types in the adult human body
External links
