Melanocytes are

melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

-producing

neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

-derived cells located in the bottom layer (the

stratum basale The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...

) of the skin's

epidermis 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 rele ...

, the middle layer of the eye (the

uvea The uvea (; Lat. ''uva'', "grape"), also called the ''uveal layer'', ''uveal coat'', ''uveal tract'', ''vascular tunic'' or ''vascular layer'' is the pigmented middle of the three concentric layers that make up an eye. History and etymolog ...

), the

inner ear The inner ear (internal ear, auris interna) is the innermost part of the vertebrate ear. In vertebrates, the inner ear is mainly responsible for sound detection and balance. In mammals, it consists of the bony labyrinth, a hollow cavity in the ...

vaginal epithelium The vaginal epithelium is the inner lining of the vagina consisting of multiple layers of (squamous) cells. The basal membrane provides the support for the first layer of the epithelium-the basal layer. The intermediate layers lie upon the basal ...

meninges In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in th ...

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

s, and

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...

. Melanin is a dark

pigment A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic compo ...

primarily responsible for

skin color Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics (inherited from one's biological parents and or individu ...

. Once synthesized, melanin is contained in special

organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...

s called

melanosome A melanosome is an organelle found in animal cells and is the site for synthesis, storage and transport of melanin, the most common light-absorbing pigment found in the animal kingdom. Melanosomes are responsible for color and photoprotection i ...

s which can be transported to nearby

keratinocyte Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the stratum basale, basal layer (''str ...

s to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against

UV radiation Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...

. Melanocytes also have a role in the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

Function

Micrograph of melanocytes in the epidermis

Through a process called melanogenesis, melanocytes produce

, which is a pigment found in the

skin 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. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

, eyes,

hair Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals. The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and f ...

nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nasal c ...

, and

. This melanogenesis leads to a long-lasting pigmentation, which is in contrast to the pigmentation that originates from oxidation of already-existing melanin. There are both basal and activated levels of melanogenesis; in general, lighter-skinned people have low basal levels of melanogenesis. Exposure to UV-B radiation causes increased melanogenesis. The purpose of melanogenesis is to protect the

hypodermis The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macro ...

, the layer under the skin, from damage by UV radiation. The color of the melanin is black, allowing it to absorb a majority of the UV light and block it from passing through the epidermis. Since the action spectrum of

sunburn Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and animals include: red or reddish skin that is ho ...

and melanogenesis are virtually identical, they are assumed to be induced by the same mechanism. The agreement of the action spectrum with the absorption spectrum of DNA points towards the formation of

cyclobutane pyrimidine dimer Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions, commonly associated with direct DNA damage. Ultraviolet light (UV; particularly UVB) induces the formation of covalent linkages betwe ...

s (CPDs) -

direct DNA damage Direct may refer to: Mathematics * Directed set, in order theory * Direct limit of (pre), sheaves * Direct sum of modules, a construction in abstract algebra which combines several vector spaces Computing * Direct access (disambiguation), ...

. Typically, between 1000 and 2000 melanocytes are found per square millimeter of skin or approximately 5% to 10% of the cells in the basal layer of epidermis. Although their size can vary, melanocytes are typically 7 μm in length. The difference in

between lightly and darkly pigmented individuals is due not to the number (quantity) of melanocytes in their skin, but to the melanocytes' level of activity (quantity and relative amounts of

eumelanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amin ...

and

pheomelanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

). This process is under hormonal control, including the MSH and ACTH peptides that are produced from the precursor proopiomelanocortin.

Vitiligo Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmen ...

is a skin disease where people lack melanin in certain areas in the skin. People with oculocutaneous

albinism Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...

typically have a very low level of melanin production. Albinism is often but not always related to the ''TYR'' gene coding the

tyrosinase Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxylat ...

enzyme. Tyrosinase is required for melanocytes to produce melanin from the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

. Albinism may be caused by a number of other genes as well, like ''OCA2'', ''SLC45A2'', ''TYRP1'', and ''HPS1'' to name some. In all, already 17 types of oculocutaneous albinism have been recognized. Each gene is related to different protein having a role in pigment production. People with

Chédiak–Higashi syndrome Chédiak–Higashi syndrome (CHS) is a rare autosomal recessive disorder that arises from a mutation of a lysosomal trafficking regulator protein, which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogeni ...

have a buildup of melanin granules due to abnormal function of

microtubules Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

Role in the immune system

In addition to their role as UV radical scavengers, melanocytes are also part of the immune system, and are considered to be immune cells. Although the full role of melanocytes in immune response is not fully understood, melanocytes share many characteristics with

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

s: branched morphology;

phagocytic Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...

capabilities; presentation of

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s to

T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

; and production and release of

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

s. Although melanocytes are dendritic in form and share many characteristics with dendritic cells, they are derived from two different cell lineages. Dendritic cells are derived from

hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within t ...

s in the

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

. Melanocytes on the other hand originate from

neural crest cells Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, Per ...

. As such, although morphologically and functionally similar, melanocytes and dendritic cells are not the same. Melanocytes are capable of expressing

MHC Class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial ce ...

, a type of MHC expressed only by certain antigen presenting cells of the immune system, when stimulated by interactions with antigen or cytokines. All cells in any given vertebrate express MHC, but most cells only express

MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on plat ...

. The other class of MHC, Class II, is found only on "professional" antigen presenting cells such as dendritic cells,

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s, and melanocytes. Importantly, melanocytes stimulated by cytokines express surface proteins such as

CD40 Cluster of differentiation 40, CD40 is a costimulatory protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on T helper cell, TH cells to CD40 activates antigen presenting cells and induces a ...

and

ICAM1 ICAM-1 (Intercellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) is a protein that in humans is encoded by the ''ICAM1'' gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial ...

in addition to MHC class II, allowing for co-stimulation of T cells. In addition to presenting antigen, one of the roles of melanocytes in the immune response is cytokine production. Melanocytes express many proinflammatory cytokines including IL-1, IL-3, IL-6, IL-8,

TNF-α Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

, and

TGF-β Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...

. Like other immune cells, melanocytes secrete these cytokines in response to activation of

Pattern Recognition Receptors Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of ...

(PRRs) such as Toll Like Receptor 4 (TLR4) which recognize MAMPs. MAMPs, also known as PAMPs, are microbial associated molecular patterns, small molecular elements such as proteins, carbohydrates, and lipids present on or in a given pathogen. In addition, cytokine production by melanocytes can be triggered by cytokines secreted by other nearby immune cells. Melanocytes are ideally positioned in the

to be sentinels against harmful pathogens. Melanocytes reside in the

, the lowest layer of the

, but they use their dendrites to interact with cells in other layers, and to capture pathogens that enter the epidermis. Melanocytes likely work in concert with both

s and

Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...

s, both of which are also actively

, to contribute to the immune response.

Melanogenesis

Tyrosine is the non-essential amino acid precursor of melanin. Tyrosine is converted to dihydroxyphenylalanine (DOPA) via the enzyme tyrosinase. Then DOPA is polymerized into melanin. The copper-ion based enzyme-catalyzed oxidative transformation of catechol derivative dopa to light absorbing dopaquinone to indole-5,6-qionone is clearly seen following the polymerization to melanin, the color of the pigment ranges from red to dark brown.

Stimulation

Numerous stimuli are able to alter melanogenesis, or the production of melanin by cultured melanocytes, although the method by which it works is not fully understood. Certain melanocortins have been shown in laboratory testing to have effect on appetite and sexual activity in mice.

Eicosanoid Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a s ...

retinoids The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth. Retinoids have many important functions throughout ...

oestrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activ ...

melanocyte-stimulating hormone The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating h ...

endothelin Endothelins are peptides with receptor (biochemistry), receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when gene ex ...

psoralens Psoralen (also called psoralene) is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered ...

hydantoin Hydantoin, or glycolylurea, is a heterocyclic organic compound with the formula CH2C(O)NHC(O)NH. It is a colorless solid that arises from the reaction of glycolic acid and urea. It is an oxidized derivative of imidazolidine. In a more general sen ...

forskolin Forskolin (coleonol) is a labdane diterpene produced by the plant ''Coleus barbatus'' (Blue Spur Flower). Other names include pashanabhedi, Indian coleus, makandi, HL-362, mao hou qiao rui hua. As with other members of the large diterpene class of ...

cholera toxin Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is AB5 multimeric protein complex secreted by the bacterium ''Vibrio cholerae''. CTX is responsible for the massive, watery diarrhea characteristic of cholera i ...

isobutylmethylxanthine IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine derivatives, is both a: # competitive non-selective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNFα and leukotriene synthesis, and re ...

diacylglycerol A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as sur ...

analogues, and UV irradiation all trigger melanogenesis and, in turn, pigmentation. Increased melanin production is seen in conditions where

adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...

(ACTH) is elevated, such as Addison's and

Cushing's disease Cushing's disease is one cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary (secondary hypercortisolism). This is most often as a result of a pituitary adenoma (speci ...

. This is mainly a consequence of alpha-MSH being secreted along with the hormone associated with reproductive tendencies in primates. Alpha-MSH is a cleavage product of ACTH that has an equal affinity for the MC1 receptor on melanocytes as ACTH. Melanosomes are

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

that package the chemical inside a

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

. The

s are organized as a cap protecting the nucleus of the

. When ultraviolet rays penetrate the skin and damage DNA,

thymidine Thymidine (symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. I ...

dinucleotide (pTpT) fragments from damaged DNA will trigger melanogenesis and cause the melanocyte to produce melanosomes, which are then transferred by dendrites to the top layer of keratinocytes.

Stem cells

The

precursor Precursor or Precursors may refer to: * Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...

of the melanocyte is the

melanoblast A melanoblast is a precursor cell of a melanocyte. These cells migrate from the trunk neural crest cells (in terms of axial level from neck to posterior end) dorsolaterally between the ectoderm and dorsal surface of the somites. See also *Biolog ...

. In adults, stem cells are contained in the bulge area of the

outer root sheath The outer root sheath or external root sheath of the hair follicle encloses the inner root sheath and hair shaft.James, William; Berger, Timothy; Elston, Dirk (2005) ''Andrews' Diseases of the Skin: Clinical Dermatology'' (10th ed.). Saunders. Pag ...

hair follicle The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction between h ...

s. When a hair is lost and the hair follicle regenerates, the stem cells are activated. These stem cells develop into both keratinocyte precursors and melanoblasts - and these melanoblasts supply both hair and skin (moving into the

basal layer The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...

of the

). There is additionally evidence that melanocyte stem cells are present in cutaneous nerves, with nerve signals causing these cells to differentiate into melanocytes for the skin.

Clinical significance

Melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

- Cancer affecting melanocytes *

Melanocytic tumor Melanocytic tumors are neoplasm, tumors developed from melanocytes. Types

* Melanocytic nevus * Melanocytic tumors of uncertain malignant potential * Melanoma Tumor {{med-sign-stub ...

s *

Melanocytic tumors of uncertain malignant potential Melanocytic tumors of uncertain malignant potential (MELTUMP) are melanocytic lesions in the dermis that cannot be classified by morphology as either benign naevi (moles) or malignant melanomas because the mass shows features of both. Several lesio ...

- Decreased number of melanocytes due to autoimmune destruction causing decreased melanin *

Albinism Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...

- Normal number of melanocytes, but decreased melanin production due to decreased tyrosinase activity or defective tyrosine transport *

Melasma Melasma (also known as chloasma faciei,James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . or the mask of pregnancy when present in pregnant women) is a tan or dark ...

(Chloasma) - Patchy hyperpigmentation of the skin Normal number of melanocytes with increased melanin production causing hyperpigmentation. Associated with pregnancy or oral contraceptive pill use. *

Addison disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...

Nevus depigmentosus Nevus depigmentosus is a loss of pigment in the skin which can be easily differentiated from vitiligo. Although age factor has not much involvement in the nevus depigmentosus but in about 19% of the cases these are noted at birth. Their size may h ...

References

External links

* - "Eye: fovea, RPE" * - "Integument: pigmented skin" {{Authority control Human cells Pigment cells Skin anatomy Epithelial cells