Keratinocytes
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Keratinocytes are the primary cells of the epidermis, constituting approximately 90% of its cellular population. They originate mainly in the basal layer, then differentiate and migrate toward the skin's surface, successively forming the spinous layer, granular layer, and stratum corneum (cornified layer). Their final form is corneocytes, which are anucleated cells filled with keratin proteins and surrounded by a resistant cornified envelope. Keratinocytes are not merely the building blocks of the epidermis. They participate in maintaining the hydrolipid barrier, the immune response, wound healing, protection against microorganisms and ultraviolet radiation, as well as the regulation of inflammation. Disorders of their proliferation, differentiation, or desquamation occur, among others, in psoriasis, atopic dermatitis, ichthyosis, keratosis pilaris, and some skin cancers.
Keratinocytes - what are they?
Keratinocytes are epithelial cells of the epidermis capable of synthesizing keratins, which are fibrous cytoskeletal proteins that provide cells with mechanical resistance. The name might suggest that their only role is producing keratin; however, modern dermatology regards them as active barrier, sensory, and immune cells.
The keratinocyte phenotype changes along with its location and stage of maturation:
- proliferating keratinocytes in the basal layer divide and renew the epidermis;
- differentiating keratinocytes gradually alter gene expression, cytoskeleton composition, and the type of intercellular junctions;
- corneocytes are a terminally differentiated form of keratinocytes, devoid of a nucleus and most organelles;
- activated keratinocytes appear in response to injury, infection, or inflammation, and secrete mediators that direct tissue repair and the immune response.
Keratins K5 and K14 predominate in the basal layer. Once differentiation begins, cells switch to the expression of, among others, K1 and K10. During injury, however, the production of regeneration-associated keratins increases, especially K6, K16, and K17. A change in the keratin profile is therefore a precise indicator of the cell's biological state.
Keratinocytes should not be equated with melanocytes. Melanocytes synthesize melanin and transfer it to keratinocytes in the form of melanosomes. The pigment accumulates above the keratinocyte nucleus, forming a structure that partially protects DNA from UV radiation.
Keratinocytes - where are they located?
The largest number of keratinocytes is found in the epidermis of the skin, which is a keratinized stratified squamous epithelium. The individual stages of their maturation correspond to the successive layers of the epidermis.
Epidermal layer | Form and properties of keratinocytes |
|---|---|
Basal layer | A single layer of proliferating cells attached to the basement membrane by hemidesmosomes. Stem and progenitor cells that renew the epidermis are located here. |
Spinous layer | Cells connected by numerous desmosomes, which give them a "spiny" appearance under microscopic examination. Intensive synthesis of structural proteins and barrier components begins. |
Granular layer | Flattening keratinocytes containing keratohyalin granules and lamellar bodies. Filaggrin, loricrin, and other components of the cornified envelope are formed. |
Clear layer | An additional layer visible primarily in the thick epidermis of the palms and soles. |
Cornified layer | Composed of corneocytes surrounded by a lipid matrix. Cells are gradually removed from the surface through the process of desquamation. |
Keratinocytes also occur in the epithelia covering certain mucosal surfaces, including within the oral cavity. Cells of similar origin form structures of hair follicles, sebaceous glands, and the nail apparatus. Within the hair follicle, there are distinct stem cell niches that participate in the hair growth cycle and can support epidermal regeneration after injury.
The epidermis does not contain blood vessels. Keratinocytes of the basal layer receive oxygen and nutrients via diffusion from the vascularized dermis across the basement membrane.
Keratinocytes - what is their role in the epidermis?
The most important task of keratinocytes is to create an epidermal barrier that limits water loss and the penetration of potentially harmful substances. This barrier is often described as a "brick and mortar" system: corneocytes correspond to the bricks, while organized intercellular lipids, primarily ceramides, cholesterol, and free fatty acids, form the mortar.
Keratinocyte functions include:
- mechanical protection, provided by keratin filaments, desmosomes, and the cornified envelope;
- control of transepidermal water loss, dependent on the proper organization of the stratum corneum and lipids;
- production of natural moisturizing factor, whose components are formed, among others, during the breakdown of filaggrin;
- formation of tight junctions, especially in the stratum granulosum, restricting intercellular transport;
- antimicrobial protection through the secretion of defensins, cathelicidin LL-37, and other antimicrobial peptides;
- threat recognition using receptors that detect microbial components and damage signals;
- immune regulation via cytokines, chemokines, and growth factors, including IL-1, IL-6, TNF, TSLP, and IL-33;
- participation in pigmentation, as keratinocytes receive melanosomes from melanocytes and influence melanocyte activity through paracrine signals;
- wound healing, consisting of shape change, migration, proliferation, and the restoration of epidermal continuity.
Terminal differentiation of the keratinocyte, referred to as cornification, is a specialized cellular program. It involves the loss of the nucleus and organelles, cross-linking of cornified envelope proteins, and the extrusion of lipids to the outside of the cell. This is not simple cell "death." The process remains strictly controlled by calcium concentration, enzyme activity, gene expression of the epidermal differentiation complex, and local immune signals.
Disruptions of these mechanisms have clinical significance. In psoriasis, keratinocyte proliferation and differentiation are accelerated and incomplete. In atopic dermatitis, abnormalities in filaggrin, lipids, and inflammatory signaling weaken the barrier. Mutations in keratin proteins can lead to genodermatoses characterized by excessive epidermal fragility.
Keratinocytes - how long does their life cycle last?
The keratinocyte life cycle includes proliferation in the basal layer, migration through the viable epidermal layers, cornification, and the residence time in the stratum corneum before desquamation. In normal human skin, the full journey from a progenitor cell to the shedding of a corneocyte takes on average approximately 4-8 weeks. Values around 39-56 days are often cited in the literature, but there is no single constant number that applies to all skin and every individual.
The popular statement that the epidermis renews itself exactly every 28 days is a simplification. The result depends on whether one evaluates the transit time through the viable epidermal layers, the residence time of corneocytes in the stratum corneum, or the entire cycle from cell division to desquamation.
The rate of renewal is influenced by:
- anatomical site and epidermal thickness;
- age and hormonal status;
- epidermal barrier integrity;
- injuries and the healing process;
- UV radiation and chronic oxidative stress;
- inflammation, infections, and dermatological diseases;
- use of retinoids, cytostatic drugs, and exfoliating procedures.
In psoriasis, cell transit through the epidermis can be shortened to a few days, resulting in incomplete differentiation and the presence of nuclei in the stratum corneum, referred to as parakeratosis. Conversely, aging, certain metabolic disorders, and chronic barrier impairment can lead to slower and less organized renewal.
Desquamation of corneocytes is an enzymatic process. It requires the controlled degradation of corneodesmosomes, which are structures connecting the cells of the stratum corneum. Its course depends, among other factors, on hydration and the acidic pH of the skin surface. Both excessive acceleration and inhibition of this process can impair barrier function.
Keratinocytes and cosmetological and aesthetic medicine procedures
Healthy keratinocytes do not need to be "stimulated" without indication. The goal of the procedures is the controlled modification of epidermal exfoliation, regeneration, or organization, rather than permanently accelerating its cycle. Treatments available at Ambasada Urody that directly or indirectly affect the epidermis and keratinocytes include:
- manual cleansing, cavitation peeling, nanopeelings, and enzymatic peeling, acting primarily within the superficial stratum corneum;
- microdermabrasion, hydradermabrasion, HydraFacial, DermaClear, and Geneo X, combining the controlled removal of corneocytes with cleansing, hydration, or the application of active substances;
- acid peels, including DermaQuest and BioRePeelCl3 procedures, which regulate stratum corneum cohesion and, depending on the formulation, induce controlled epidermal renewal;
- carbon peeling, utilizing a carbon formulation and laser energy for superficial cleansing and exfoliation;
- medical peels: TCA, Perfect Peel, VI Peel, Cosmelan, and Dermamelan, used for specific indications such as photodamage, keratinization disorders, and hyperpigmentation;
- Dermapen 4.0, Dermapen 4.0 with exosomes, microneedle and nanoneedle mesotherapy, and Dermapen 4.0 with platelet-rich plasma, which trigger a repair response in keratinocytes and the dermis through controlled micro-injuries;
- ablative and non-ablative fractional laser, and hybrid lifting, which, depending on the technology, cause microscopic zones of ablation or thermal damage and subsequent re-epithelialization;
- oxygen infusion and LED therapy, used primarily as supportive procedures for skincare, soothing inflammation, or post-treatment regeneration.
Procedures that disrupt the epidermal barrier require individual qualification. Active infection, herpes simplex, skin damage, uncontrolled dermatosis, certain medications, and a tendency toward post-inflammatory hyperpigmentation may constitute a contraindication or require adjusting treatment parameters. Following intensive exfoliation, microneedling, or laser therapy, gentle barrier care and photoprotection are of fundamental importance.