Corneocyte

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Corneocytes are terminally differentiated keratinocytes and compose most of the stratum corneum, the outermost layer of the epidermis. They are regularly replaced through desquamation and renewal from lower epidermal layers and are essential for its function as a skin barrier.

Contents

Structure

Corneocytes are keratinocytes without nuclei and cytoplasmic organelles. [1] They contain a highly insoluble cornified envelope within the plasma membrane, and lipids (fatty acids, sterols and ceramides) released from lamellar bodies within the epidermis. The corneocytes are interlocked with each other and organized as vertical columns of 10–30 cells to form the stratum corneum. [2]

Corneocytes in the lower part of the stratum corneum are bridged together through specialized junctions (corneodesmosomes). Those junctions disintegrate as corneocytes migrate toward the surface of the skin and result in desquamation. At the same time, as those loosened junctions encounter more hydration, they will expand and connect together, forming potential entry pores for microorganisms. [2]

The stratum corneum can absorb three times its weight in water, but if its water content drops below 10%, it no longer remains pliable and cracks. [3]

Formation

Corneocytes are keratinocytes in their last stage of differentiation. Keratinocytes in the stratum basale of the epidermis will multiply through cell division and migrate toward the skin surface. During that migration keratinocytes will undergo multiple stages of differentiation to finally become corneocytes once they reach the stratum corneum. As corneocytes are continually eliminated through desquamation or through rubbing, skin washing or detergents they are also continually formed through keratinocyte differentiation. [4]

Corneocytes, also referred to as squames (from Latin squama, meaning a "thin flake" or "scales") are terminally differentiated, anucleated cells of keratinocyte lineage that constitute the majority of stratum corneum, the outermost layer of the epidermis. Size of a corneocyte is approximately 30-50 μm in diameter and 1 μm thick, and the average area of corneocytes at the surface of the skin reaches approximately 1000 μm2, but may vary according to anatomical location, age and external environmental conditions such as ultraviolet (UV) irradiation. [5] [6] Major constituents of corneocytes are keratin intermediate filaments organized in parallel bundles to form a matrix to give rigidity to the overall structure of the skin. [7]

Functions

Layers of corneocytes produce high mechanical strength which allows epidermis of the skin to perform its function as a physical, chemical and immunological barrier. For example, corneocytes act as UV barrier by reflecting the scattered UV radiation, protecting cells inside the body from apoptosis and DNA damage. [8] As corneocytes are essentially dead cells, they are not prone to viral attacks, though invisible microabrasions may cause permeability. Colonization of pathogens in the skin is prevented via complete turnovers of corneocyte layer every 2–4 weeks. [9] Corneocytes are also capable of absorbing and storing small amounts of water to keep the skin hydrated and maintain its flexibility. [10]

Intracellular structures

Natural moisturizing factor

Corneocytes contain small molecules called natural moisturizing factors, which absorb small amounts of water into the corneocytes thereby hydrating the skin. The natural moisturizing factor is a collection of water-soluble compounds produced from the degradation of histidine-rich proteins called filaggrin, which are responsible for aggregating keratin filaments to form keratin bundles that maintain the rigid structure of the cells in stratum corneum. [11] When filaggrin is degraded, urea, pyrrolidone carboxylic acid (1,2), glutamic acid and other amino acids are produced. [12] These are collectively referred to as the natural moisturizing factor of the skin. The components of the natural moisturizing factor absorb water from the atmosphere to ensure that the superficial layers of the stratum corneum stay hydrated. [13] As they are water-soluble themselves, excessive water contact may leach them and inhibit their normal functions which is why prolonged contact with water makes the skin drier. [14] The intercellular lipid layer helps prevent the loss of natural moisturizing factor by sealing the outside of each corneocyte. [12]

Extracellular structures

Although stratum corneum is mostly composed of corneocytes, other supporting structures are present in the extracellular matrix to assist in the function of stratum corneum. [15] These include:

Lamellar bodies

Lamellar bodies are tubular or ovoid-shaped secretory organelles derived from the Golgi apparatus of keratinocytes in the upper part of stratum spinosum. [16] From the site of production, lamellar bodies migrate to the top of the stratum granulosum and then into the intercellular domain of the stratum corneum to extrude their contents, which are predominantly lipids. The lipids ultimately form the lamellar lipid bilayer that surrounds corneocytes and also contributes to the permeability barrier homeostasis of the stratum corneum. [12] The homeostasis function is regulated by the calcium gradient in the epidermis. [17] Usually the calcium level is very low in stratum corneum, but high in stratum granulosum. Once the permeability barrier is disrupted an influx of water occurs in the stratum corneum, which in turn increases the calcium levels in the stratum corneum but decreases it in the stratum granulosum. This perturbation induces lamellar bodies to undergo exocytosis and secrete lipids such as glycosylceramides, cholesterol and phospholipids to retrieve the permeability barrier function of stratum corneum. [8]

Intercellular lipids (lamellar lipid bilayer)

Corneocytes are embedded in a matrix of specialized lipids that constitute approximately 20% of the stratum corneum volume. [7] The major constituents of the intercellular lipids in stratum corneum include ceramides (30-50% by mass), cholesterol (25% by mass) and free fatty acids (10-20% by mass), mostly produced by lamellar bodies. [8] [18] These hydrophobic components fuse together to form multiple bilayers of lipids between corneocytes to act as the principal barrier to the transcutaneous movement of water and electrolytes.

Cornified envelope

The cornified envelope is a protein shell that surrounds each corneocyte. Its thickness varies between 15 and 20 nm. [19] The highly insoluble cornified envelope is formed by cross-linking of soluble precursor proteins such as loricrin, involucrin, envoplakin and periplakin. [20]

Corneodesmosomes and desquamation

The overall integrity of the stratum corneum is maintained by specialized intercellular proteins called corneodesmosomes. [21] Three adhesive proteins desmoglein-1, desmocollin-1 and corneodesmosin compose the corneodesmosomes and provide the cohesive forces to connect the adjacent corneocytes. [22] The components of the corneodesmosomes are gradually degraded by the enzymes that digest proteins, [22] as the corneocytes are pushed towards the surface of the skin. As a result of the weakened corneodesmosomes in the outer skin surface, the uppermost layers of corneocytes get exfoliated through frictional forces such as rubbing or washing. This process is a normal protective mechanism of the skin to prevent pathogens from colonizing the skin, and is referred to as desquamation. In healthy skin, desquamation is an invisible process and the stratum corneum is turned over completely within 2–4 weeks, while maintaining the tissue thickness. [9]

Pathologies

Dry skin (xerosis)

Dry skin (xerosis) involves increased thickness of stratum corneum (hyperkeratosis), which may occur due to various reasons including aging, humidity of the environment or UV irradiation. The accumulation of corneocyte clumps on the surface of the skin may lead to abnormal detachment of squames as visible clusters. Xerosis is common, especially in elderly individuals [23] which may be due to decreased quantity of free amino acids, a constituent of natural moisturizing factor. [24] Consequently, many moisturizers in the markets incorporate the components of the natural moisturizing factor as well as keratin and elastin. [25]

Localization

Corneocytes are part of the stratum corneum of the epidermis and contribute to the barrier function of the skin. [26]

See also

Related Research Articles

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Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.

<span class="mw-page-title-main">Keratinocyte</span> Primary type of cell found in the epidermis

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. Basal cells in the basal layer of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually being shed, which happens every 40 to 56 days in humans.

<span class="mw-page-title-main">Epidermis</span> Outermost of the three layers that make up the skin

The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water released from the body into the atmosphere through transepidermal water loss.

<span class="mw-page-title-main">Vernix caseosa</span> Waxy white substance found coating the skin of newborn human babies

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<span class="mw-page-title-main">Stratum corneum</span> Outermost layer of the epidermis

The stratum corneum is the outermost layer of the epidermis. Consisting of dead tissue, it protects underlying tissue from infection, dehydration, chemicals and mechanical stress. It is composed of 15–20 layers of flattened cells with no nuclei and cell organelles.

<span class="mw-page-title-main">Desquamation</span> Medical condition

Desquamation occurs when the outermost layer of a tissue, such as the skin, is shed. The term is from Latin desquamare 'to scrape the scales off a fish'.

<span class="mw-page-title-main">Stratum granulosum</span> Cell layer in the epidermis

The stratum granulosum is a thin layer of cells in the epidermis lying above the stratum spinosum and below the stratum corneum. Keratinocytes migrating from the underlying stratum spinosum become known as granular cells in this layer. These cells contain keratohyalin granules, which are filled with histidine- and cysteine-rich proteins that appear to bind the keratin filaments together. Therefore, the main function of keratohyalin granules is to bind intermediate keratin filaments together.

<span class="mw-page-title-main">Lamellar bodies</span> Secretory organelles

In cell biology, lamellar bodies are secretory organelles found in type II alveolar cells in the lungs, and in keratinocytes in the skin. They are oblong structures, appearing about 300-400 nm in width and 100-150 nm in length in transmission electron microscopy images. Lamellar bodies in the alveoli of the lungs fuse with the cell membrane and release pulmonary surfactant into the extracellular space.

<span class="mw-page-title-main">Human skin</span> Organ covering the outside of the human body

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Keratohyalin is a protein structure found in cytoplasmic granules of the keratinocytes in the stratum granulosum of the epidermis. Keratohyalin granules (KHG) mainly consist of keratin, profilaggrin, loricrin and trichohyalin proteins which contribute to cornification or keratinization, the process of the formation of epidermal cornified cell envelope. During the keratinocyte differentiation, these granules maturate and expand in size, which leads to the conversion of keratin tonofilaments into a homogenous keratin matrix, an important step in cornification.

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Involucrin is a protein component of human skin and in humans is encoded by the IVL gene. In binding the protein loricrin, involucrin contributes to the formation of a cell envelope that protects corneocytes in the skin.

<span class="mw-page-title-main">KLK7</span> Protein-coding gene in the species Homo sapiens

Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the KLK7 gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13).

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<span class="mw-page-title-main">Topical cream formulation</span>

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References

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  12. 1 2 3 Robinson M, Visscher M, Laruffa A, Wickett R (2010). "Natural moisturizing factors (NMF) in the stratum corneum (SC). I. Effects of lipid extraction and soaking". Journal of Cosmetic Science. 61 (1): 13–22. PMID   20211113.
  13. ↑ Osseiran, Sam; Cruz, Jomer Dela; Jeong, Sinyoung; Wang, Hequn; Fthenakis, Christina; Evans, Conor L. (2018-12-01). "Characterizing stratum corneum structure, barrier function, and chemical content of human skin with coherent Raman scattering imaging". Biomedical Optics Express. 9 (12): 6425–6443. doi:10.1364/BOE.9.006425. ISSN   2156-7085. PMC   6490993 . PMID   31065440.
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  15. ↑ Elias, Peter M.; Wakefield, Joan S. (October 2014). "Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis". Journal of Allergy and Clinical Immunology. 134 (4): 781–791.e1. doi:10.1016/j.jaci.2014.05.048. PMC   4186911 . PMID   25131691.
  16. ↑ Tarutani M, Nakajima K, Uchida Y, Takaishi M, Goto-Inoue N, Ikawa M, Setou M, Kinoshita T, Elias PM, Sano S, Maeda Y (2012). "GPHR-dependent functions of the Golgi apparatus are essential for the formation of lamellar granules and the skin barrier". The Journal of Investigative Dermatology. 132 (8): 2019–25. doi: 10.1038/jid.2012.100 . PMID   22572823.
  17. ↑ Feingold KR (2007). "Thematic review series: skin lipids. The role of epidermal lipids in cutaneous permeability barrier homeostasis". Journal of Lipid Research. 48 (12): 2531–46. doi: 10.1194/jlr.R700013-JLR200 . PMID   17872588.
  18. ↑ Squier CA, Cox P, Wertz PW (1991). "Lipid content and water permeability of skin and oral mucosa". The Journal of Investigative Dermatology. 96 (1): 123–6. doi: 10.1111/1523-1747.ep12515931 . PMID   1987287.
  19. ↑ Jarnik M, Simon MN, Steven AC (April 1998). "Cornified cell envelope assembly: a model based on electron microscopic determinations of thickness and projected density". Journal of Cell Science. 111 ( Pt 8) (8): 1051–60. doi:10.1242/jcs.111.8.1051. PMID   9512501.
  20. ↑ Sevilla LM, Nachat R, Groot KR, Klement JF, Uitto J, Djian P, Määttä A, Watt FM (December 2007). "Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier" (PDF). The Journal of Cell Biology. 179 (7): 1599–612. doi:10.1083/jcb.200706187. PMC   2373502 . PMID   18166659.
  21. ↑ Del Rosso, James Q.; Levin, Jacqueline (September 2011). "The clinical relevance of maintaining the functional integrity of the stratum corneum in both healthy and disease-affected skin". The Journal of Clinical and Aesthetic Dermatology. 4 (9): 22–42. ISSN   2689-9175. PMC   3175800 . PMID   21938268.
  22. 1 2 Caubet C, Jonca N, Brattsand M, Guerrin M, Bernard D, Schmidt R, Egelrud T, Simon M, Serre G (2004). "Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7". The Journal of Investigative Dermatology. 122 (5): 1235–44. doi: 10.1111/j.0022-202X.2004.22512.x . PMID   15140227.
  23. ↑ Reamy BV, Bunt CW, Fletcher S (2011). "A diagnostic approach to pruritus". American Family Physician. 84 (2): 195–202. PMID   21766769.
  24. ↑ Horii I, Nakayama Y, Obata M, Tagami H (1989). "Stratum corneum hydration and amino acid content in xerotic skin". The British Journal of Dermatology. 121 (5): 587–92. doi:10.1111/j.1365-2133.1989.tb08190.x. PMID   2597631. S2CID   19157179.
  25. ↑ "Natural Skin Care Routine You Need To Know To Start". kinivalo.com.bd. Retrieved 2023-06-23.
  26. ↑ Murphrey, Morgan B.; Miao, Julia H.; Zito, Patrick M. (2023), "Histology, Stratum Corneum", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30020671 , retrieved 2023-06-23

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