Melanocytes are

melanin Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes. There are ...

-producing

neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...

-derived

cells Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a d ...

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 cuboida ...

) 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 Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

, the middle layer of the

eye An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system. In higher organisms, the ey ...

(the

uvea The uvea (; derived from meaning "grape"), also called the uveal layer, uveal coat, uveal tract, vascular tunic or vascular layer, is the pigmented middle layer of the three concentric layers that make up an eye, precisely between the inne ...

), 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 (Epithelium, squamous) cells. The basal membrane provides the support for the first layer of the epithelium-the basal layer. The intermediate layers lie u ...

meninges In anatomy, the meninges (; meninx ; ) 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 the subarachnoid spac ...

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

s, and

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

found in many

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

s and

bird Birds are a group of warm-blooded vertebrates constituting the class (biology), class Aves (), characterised by feathers, toothless beaked jaws, the Oviparity, laying of Eggshell, hard-shelled eggs, a high Metabolism, metabolic rate, a fou ...

s. Melanin is a dark

pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub ...

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 largely the result of genetics (inherited from one's biological parents), and in ...

. Once synthesized, melanin is contained in special

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

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 photoprotectio ...

s which can be transported to nearby

keratinocyte 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 (''stratum basale'') of the skin are sometimes referre ...

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 radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of t ...

. Melanocytes also have a role in the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

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 animal coverings, such as the arthropod exoskeleton, have different ...

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 ...

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 nas ...

, 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, or 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 ...

, 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 other animals include red or reddish skin tha ...

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 represent molecular lesions originating from thymine or cytosine bases within DNA, resulting from photochemical reactions. These lesions, commonly linked to direct DNA damage, are induced by ultraviolet light (UV), particularly ...

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), a ...

. 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. Both lightly and darkly pigmented skin contain similar numbers of melanocytes, with difference in

due to differences the packing of

eumelanin Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes. There are ...

into the

s of

s: those in dark-toned skin are "packaged into peri-nuclear distributed, ellipsoid" melanosomes while those light-tone skin are "assembled into clustered small, circular melanosomes". There are also differences in the quantity and relative amounts of

and

pheomelanin Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the Biological pigment, pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melan ...

. Pigmentation including tanning is under hormonal control, including the MSH and ACTH peptides that are produced from the precursor proopiomelanocortin.

Vitiligo Vitiligo (, ) is a chronic autoimmune disorder that causes patches of skin to lose pigment or color. The cause of vitiligo is unknown, but it may be related to immune system changes, genetic factors, stress, or sun exposure, and susceptibili ...

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 reddish pink or blue eyes. Individuals with the condition are referred to as albinos. Varied use and interpretation of ...

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 hydroxy ...

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 over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

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 conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

. 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 pyogenic ...

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 A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's 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 (biology), 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 ph ...

capabilities; presentation of

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, 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 T cells (also known as T lymphocytes) are an important part 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 receptor (TCR) on their cell ...

; 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 produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s. Although melanocytes are dendritic in form and share many characteristics with dendritic cells, they derive from 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 first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the ...

s in the

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, 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 i ...

. Melanocytes on the other hand originate from

neural crest cells The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, an ...

. 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, macrophages, some endothelial cells, thymic epithelial cells, and B cell ...

, 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 ...

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

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

B cell B cells, also known as B lymphocytes, are a type 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 inserted into the plasm ...

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

CD40 Cluster of differentiation 40, CD40 is a type I transmembrane 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 i ...

and

ICAM1 ICAM-1 (Intercellular adhesion molecule, 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 ty ...

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), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

, 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 ...

. 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 th ...

(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. They 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. They likely work in concert with both

s and

Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin once thought to be a resident dendritic cell. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in t ...

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 -Dopaquinone also known as ''o''-dopaquinone is a metabolite of L-DOPA (L-dihydroxyphenylalanine) and a precursor of melanin. Biosynthesis of melanin occurs in melanocytes Melanocytes are melanin-producing neural crest-derived cells locat ...

indole-5,6-quinone Indole-5,6-quinone is an indolequinone, a chemical compound found in the oxidative browning reaction of fruits like bananas where it is mediated by the tyrosinase type polyphenol oxidase from tyrosine and catecholamines leading to the formation o ...

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. 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 ...

(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 (spec ...

. 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 a neuron, synaptic vesicles (or neurotransmitter vesicles) s ...

that package the chemical inside a

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

. The

s are organized as a cap protecting the nucleus of the

. When ultraviolet rays penetrate the skin and damage DNA,

thymidine Thymidine (nucleoside#List of nucleosides and corresponding nucleobases, symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine nucleoside, deoxynucleoside. Deoxythymidine is the DNA nuc ...

dinucleotide (pTpT) fragments from damaged

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

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), hypothesized genus of fossil birds that was composed of fossilized parts of unre ...

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 *Biolo ...

. 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. Page ...

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 betwee ...

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 cuboida ...

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 is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

- Cancer affecting melanocytes * Melanocytic tumors * Melanocytic tumors of uncertain malignant potential *

- 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 reddish pink or blue eyes. Individuals with the condition are referred to as albinos. Varied use and interpretation of ...

- 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 dar ...

(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 *

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