Editing Melanocyte

{{short description|Melanin-producing cells of the skin}}
{{human-centric}}
{{Infobox cell
| Name        = Melanocyte
| Latin       = melanocytus
| Image       = Illu skin02.jpg
| Caption     = Melanocyte and [[melanin]]
| Width       =
| Image2      =
| Caption2    =
| System      =
| Location = [[Skin]]
| Precursor = [[Neural crest]]
| Function = [[Melanin]] production
| Pronunciation = {{IPAc-en|audio=En-melanocyte.oga|m|ə|ˈ|l|æ|n|ə|ˌ|s|aɪ|t|,_|-|n|oʊ|-}} or {{IPAc-en|ˈ|m|ɛ|l|ə|n|ə|ˌ|s|aɪ|t|,_|-|n|oʊ|-}}{{refn|{{Cite encyclopedia |url=http://www.lexico.com/definition/Melanocyte |archive-url=https://web.archive.org/web/20200322182200/https://www.lexico.com/definition/melanocyte |url-status=dead |archive-date=2020-03-22 |title=Melanocyte |dictionary=[[Lexico]] UK English Dictionary |publisher=[[Oxford University Press]]}} }}{{refn|{{MerriamWebsterDictionary|Melanocyte}}}}
}}
'''Melanocytes''' are [[melanin]]-producing [[neural-crest|neural crest]]-derived<ref>{{cite journal | vauthors = Cramer SF | title = The origin of epidermal melanocytes. Implications for the histogenesis of nevi and melanomas | journal = Archives of Pathology & Laboratory Medicine | volume = 115 | issue = 2 | pages = 115–9 | date = February 1991 | pmid = 1992974 }}</ref> [[cell (biology)|cells]] located in the bottom layer (the [[stratum basale]]) of the skin's [[epidermis (skin)|epidermis]], the middle layer of the [[eye]] (the [[uvea]]),<ref name=pmid6616275>
{{cite journal | vauthors = Barden H, Levine S | title = Histochemical observations on rodent brain melanin | journal = Brain Research Bulletin | volume = 10 | issue = 6 | pages = 847–51 | date = June 1983 | pmid = 6616275 | doi = 10.1016/0361-9230(83)90218-6 | s2cid = 4783099 }}</ref> the [[inner ear]],<ref name=pmid17247639>
{{cite journal | vauthors = Markert CL, Silvers WK | title = The Effects of Genotype and Cell Environment on Melanoblast Differentiation in the House Mouse | journal = Genetics | volume = 41 | issue = 3 | pages = 429–50 | date = May 1956 | doi = 10.1093/genetics/41.3.429 | pmid = 17247639 | pmc = 1209793 }}</ref> [[vaginal epithelium]],<ref>{{Cite book|url=https://books.google.com/books?id=3lEtAxpNLewC&pg=SA2-PA29-IA2|title=Modern Colposcopy Textbook and Atlas | vauthors = Mayeaux EJ, Cox JT | collaboration = American Society for Colposcopy and Cervical Pathology |date=2011-12-28|publisher=Lippincott Williams & Wilkins|isbn=9781451153835|language=en}}</ref> [[meninges]],<ref name=pmid4940552>
{{cite journal | vauthors = Mintz B | title = Clonal basis of mammalian differentiation | journal = Symposia of the Society for Experimental Biology | volume = 25 | pages = 345–70 | year = 1971 | pmid = 4940552 }}</ref> [[bone]]s,<ref name=pmid14426921>
{{cite journal | vauthors = Nichols SE, Reams WM | title = The occurrence and morphogenesis of melanocytes in the connective tissues of the PET/MCV mouse strain | journal = Journal of Embryology and Experimental Morphology | volume = 8 | pages = 24–32 | date = March 1960 | pmid = 14426921 }}</ref> and [[heart]] found in many [[mammal]]s and [[bird]]s.<ref name=pmid5476812>
{{cite journal | vauthors = Theriault LL, Hurley LS | title = Ultrastructure of developing melanosomes in C57 black and pallid mice | journal = Developmental Biology | volume = 23 | issue = 2 | pages = 261–75 | date = October 1970 | pmid = 5476812 | doi = 10.1016/0012-1606(70)90098-9 }}</ref> Melanin is a dark [[pigment]] primarily responsible for [[skin color]]. Once synthesized, melanin is contained in special [[organelle]]s called [[melanosome]]s which can be transported to nearby [[keratinocyte]]s to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against [[Ultraviolet|UV radiation]]. Melanocytes also have a role in the [[immune system]].

== Function ==
[[File:Blausen 0632 Melanocyte.png|thumb|Illustration of a melanocyte]]
[[File:Micrograph of melanocytes in the epidermis.jpg|thumb|Micrograph of melanocytes in the epidermis]]
Through a process called melanogenesis, melanocytes produce [[melanin]], which is a pigment found in the [[human skin|skin]], [[human eye|eye]]s, [[hair]], [[nasal cavity]], and [[inner ear]]. 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 [[Subcutaneous tissue|hypodermis]], 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.<ref name=Agar2005>
{{cite journal | vauthors = Agar N, Young AR | title = Melanogenesis: a photoprotective response to DNA damage? | journal = Mutation Research | volume = 571 | issue = 1–2 | pages = 121–32 | date = April 2005 | pmid = 15748643 | doi = 10.1016/j.mrfmmm.2004.11.016 | bibcode = 2005MRFMM.571..121A }}</ref>

Since the action spectrum of [[sunburn]] and melanogenesis are virtually identical, they are assumed to be induced by the same mechanism.<ref name=Parrish1982>
{{cite journal | vauthors = Parrish JA, Jaenicke KF, Anderson RR | title = Erythema and melanogenesis action spectra of normal human skin | journal = Photochemistry and Photobiology | volume = 36 | issue = 2 | pages = 187–91 | date = August 1982 | pmid = 7122713 | doi = 10.1111/j.1751-1097.1982.tb04362.x | s2cid = 38940583 }}</ref> The agreement of the action spectrum with the absorption spectrum of DNA points towards the formation of [[cyclobutane pyrimidine dimer]]s (CPDs) - [[direct DNA damage]].

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,<ref name="Tadokoro Yamaguchi Batzer Coelho 2005 pp. 1326–1332">{{cite journal |last1=Tadokoro |first1=Taketsugu |last2=Yamaguchi |first2=Yuji |last3=Batzer |first3=Jan |last4=Coelho |first4=Sergio G. |last5=Zmudzka |first5=Barbara Z. |last6=Miller |first6=Sharon A. |last7=Wolber |first7=Rainer |last8=Beer |first8=Janusz Z. |last9=Hearing |first9=Vincent J. |year=2005 |title=Mechanisms of Skin Tanning in Different Racial/Ethnic Groups in Response to Ultraviolet Radiation |journal=Journal of Investigative Dermatology |publisher=Elsevier BV |volume=124 |issue=6 |pages=1326–1332 |doi=10.1111/j.0022-202x.2005.23760.x |issn=0022-202X|doi-access=free |pmid=15955111 }}</ref> with difference in [[Human skin color|skin color]] due to differences the packing of [[eumelanin]] into the [[melanosome]]s of [[keratinocyte]]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".<ref name="Greaves 2014 p. 20132955">{{cite journal |last=Greaves |first=Mel |date=2014-04-22 |title=Was skin cancer a selective force for black pigmentation in early hominin evolution? |journal=Proceedings of the Royal Society B: Biological Sciences |volume=281 |issue=1781 |page=20132955 |doi=10.1098/rspb.2013.2955 |issn=0962-8452|doi-access=free |pmid=24573849 |pmc=3953838 }}</ref> There are also differences in the quantity and relative amounts of [[eumelanin]] and [[pheomelanin]].<ref name="Greaves 2014 p. 20132955" /> Pigmentation including tanning is under hormonal control, including the [[Melanocyte-stimulating hormone|MSH]] and ACTH peptides that are produced from the precursor proopiomelanocortin.

[[Vitiligo]] is a skin disease where people lack melanin in certain areas in the skin.

People with oculocutaneous [[Albinism in humans|albinism]] typically have a very low level of melanin production. Albinism is often but not always related to the ''TYR'' gene coding the [[tyrosinase]] enzyme.  Tyrosinase is required for melanocytes to produce melanin from the [[amino acid]] [[tyrosine]].<ref>{{cite web |url=http://ghr.nlm.nih.gov/gene/TYR|title=TYR |publisher=National Institutes of Health|access-date=23 June 2013}}</ref> Albinism may be caused by a number of other genes as well, like ''OCA2'',<ref>{{cite web |url=http://ghr.nlm.nih.gov/gene/OCA2|title=OCA2 |publisher=National Institutes of Health|access-date=25 March 2016}}</ref> ''SLC45A2'',<ref>{{cite web |url=http://ghr.nlm.nih.gov/gene/SLC45A2|title=SLC45A2 |publisher=National Institutes of Health|access-date=25 March 2016}}</ref> ''TYRP1'',<ref>{{cite web |url=http://ghr.nlm.nih.gov/gene/TYRP1|title=TYRP1 |publisher=National Institutes of Health|access-date=25 March 2016}}</ref> and ''HPS1''<ref>{{cite web |url=http://ghr.nlm.nih.gov/gene/HPS1|title=HPS1 |publisher=National Institutes of Health|access-date=25 March 2016}}</ref> to name some. In all, already 17 types of oculocutaneous albinism have been recognized.<ref>{{cite journal | vauthors = Montoliu L, Grønskov K, Wei AH, Martínez-García M, Fernández A, Arveiler B, Morice-Picard F, Riazuddin S, Suzuki T, Ahmed ZM, Rosenberg T, Li W | title = Increasing the complexity: new genes and new types of albinism | journal = Pigment Cell & Melanoma Research | volume = 27 | issue = 1 | pages = 11–8 | date = January 2014 | pmid = 24066960 | doi = 10.1111/pcmr.12167 | s2cid = 7305884 | doi-access = free }}</ref> Each gene is related to different protein having a role in pigment production.

People with [[Chédiak–Higashi syndrome]] have a buildup of melanin granules due to abnormal function of [[microtubules]].

== 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.<ref name=":0">{{cite journal | vauthors = Gasque P, Jaffar-Bandjee MC | title = The immunology and inflammatory responses of human melanocytes in infectious diseases | journal = The Journal of Infection | volume = 71 | issue = 4 | pages = 413–21 | date = October 2015 | pmid = 26092350 | doi = 10.1016/j.jinf.2015.06.006 }}</ref> Although the full role of melanocytes in immune response is not fully understood, melanocytes share many characteristics with [[dendritic cell]]s: branched morphology; [[Phagocytosis|phagocytic]] capabilities; presentation of [[antigen]]s to [[T cell|T-cells]]; and production and release of [[cytokine]]s.<ref name=":0" /><ref name=":1">{{cite journal | vauthors = Plonka PM, Passeron T, Brenner M, Tobin DJ, Shibahara S, Thomas A, Slominski A, Kadekaro AL, Hershkovitz D, Peters E, Nordlund JJ, Abdel-Malek Z, Takeda K, Paus R, Ortonne JP, Hearing VJ, [[Karin Schallreuter|Schallreuter KU]] | title = What are melanocytes really doing all day long...? | journal = Experimental Dermatology | volume = 18 | issue = 9 | pages = 799–819 | date = September 2009 | pmid = 19659579 | pmc = 2792575 | doi = 10.1111/j.1600-0625.2009.00912.x }}</ref><ref>{{cite journal | vauthors = Mackintosh JA | title = The antimicrobial properties of melanocytes, melanosomes and melanin and the evolution of black skin | journal = Journal of Theoretical Biology | volume = 211 | issue = 2 | pages = 101–13 | date = July 2001 | pmid = 11419954 | doi = 10.1006/jtbi.2001.2331 | bibcode = 2001JThBi.211..101M }}</ref> 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]]s in the [[bone marrow]]. Melanocytes on the other hand originate from [[Neural crest|neural crest cells]]. 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]],<ref name=":1" /> 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]]. The other class of MHC, [[MHC class II|Class II]], is found only on "professional" antigen presenting cells such as dendritic cells, [[macrophage]]s, [[B cell]]s, and melanocytes. Importantly, melanocytes stimulated by cytokines express surface proteins such as [[CD40 (protein)|CD40]] and [[ICAM-1|ICAM1]] in addition to MHC class II, allowing for co-stimulation of T cells.<ref name=":0" />

In addition to presenting antigen, one of the roles of melanocytes in the immune response is cytokine production.<ref name=":2">{{cite journal | vauthors = Abdallah F, Mijouin L, Pichon C | title = Skin Immune Landscape: Inside and Outside the Organism | journal = Mediators of Inflammation | volume = 2017 | pages = 5095293 | date = 2017 | pmid = 29180836 | pmc = 5664322 | doi = 10.1155/2017/5095293 | doi-access = free }}</ref> Melanocytes express many proinflammatory cytokines including [[Interleukin-1 family|IL-1]], [[Interleukin 3|IL-3]], [[Interleukin 6|IL-6]], [[Interleukin 8|IL-8]], [[Tumor necrosis factor alpha|TNF-α]], and [[Transforming growth factor beta|TGF-β]].<ref name=":0" /><ref name=":1" /> Like other immune cells, melanocytes secrete these cytokines in response to activation of [[Pattern recognition receptor|Pattern Recognition Receptors]] (PRRs) such as [[TLR4|Toll Like Receptor 4]] (TLR4) which recognize [[Pathogen-associated molecular pattern|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.<ref name=":0" />

Melanocytes are ideally positioned in the [[epidermis]] to be sentinels against harmful pathogens. They reside in the [[stratum basale]],<ref name=":2" /> the lowest layer of the [[epidermis]], but they use their dendrites to interact with cells in other layers,<ref>{{cite journal | vauthors = Tapia CV, Falconer M, Tempio F, Falcón F, López M, Fuentes M, Alburquenque C, Amaro J, Bucarey SA, Di Nardo A | title = Melanocytes and melanin represent a first line of innate immunity against Candida albicans | journal = Medical Mycology | volume = 52 | issue = 5 | pages = 445–54 | date = July 2014 | pmid = 24934806 | doi = 10.1093/mmy/myu026 | doi-access = free }}</ref> and to capture pathogens that enter the epidermis.<ref name=":1" /> They likely work in concert with both [[keratinocyte]]s and [[Langerhans cell]]s,<ref name=":0" /><ref name=":1" /> both of which are also actively [[Phagocytosis|phagocytic]],<ref name=":2" /> 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
[[L-Dopaquinone|dopaquinone]] to [[indole-5,6-quinone]] is clearly seen following the polymerization to melanin, the color of the pigment ranges from red to dark brown.

====Stimulation====
{{Main|Melanocortin}}
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) is elevated, such as [[Addison's disease|Addison's]] and [[Cushing's disease]]. 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.<ref>{{cite journal | vauthors = Abdel-Malek Z, Scott MC, Suzuki I, Tada A, Im S, Lamoreux L, Ito S, Barsh G, Hearing VJ | title = The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation | journal = Pigment Cell Research | volume = 13 | pages = 156–62 | date = 2000-01-01 | issue = Suppl 8 | pmid = 11041375 | doi = 10.1034/j.1600-0749.13.s8.28.x | url = http://repository.ajou.ac.kr/handle/201003/3716 }}</ref>

Melanosomes are [[Vesicle (biology)|vesicles]] that package the chemical inside a [[plasma membrane]]. The [[melanosome]]s are organized as a cap protecting the nucleus of the [[keratinocyte]]. When ultraviolet rays penetrate the skin and damage DNA, [[thymidine]] dinucleotide (pTpT) fragments from damaged [[DNA]] will trigger melanogenesis<ref>
{{cite journal | vauthors = Eller MS, Maeda T, Magnoni C, Atwal D, Gilchrest BA | title = Enhancement of DNA repair in human skin cells by thymidine dinucleotides: evidence for a p53-mediated mammalian SOS response | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 23 | pages = 12627–32 | date = November 1997 | pmid = 9356500 | pmc = 25061 | doi = 10.1073/pnas.94.23.12627 | bibcode = 1997PNAS...9412627E | doi-access = free }}</ref> and cause the melanocyte to produce melanosomes, which are then transferred by dendrites to the top layer of keratinocytes.

=== Stem cells ===
The [[Precursor cell|precursor]] of the melanocyte is the [[melanoblast]].  In adults, stem cells are contained in the bulge area of the [[outer root sheath]] of [[hair follicle]]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 [[Stratum basale|basal layer]] of the [[epidermis]]). 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.<ref>{{cite journal | vauthors = Cichorek M, Wachulska M, Stasiewicz A, Tymińska A | title = Skin melanocytes: biology and development | journal = Postepy Dermatologii I Alergologii | volume = 30 | issue = 1 | pages = 30–41 | date = February 2013 | pmid = 24278043 | pmc = 3834696 | doi = 10.5114/pdia.2013.33376 }}</ref>

==Clinical significance==
* [[Melanoma]] - Cancer affecting melanocytes
* [[Melanocytic tumor]]s
* [[Melanocytic tumors of uncertain malignant potential]]
* [[Vitiligo]] - Decreased number of melanocytes due to autoimmune destruction causing decreased melanin
* [[Albinism in humans|Albinism]] - Normal number of melanocytes, but decreased melanin production due to decreased tyrosinase activity or defective tyrosine transport
* [[Melasma]] (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's disease|Addison disease]]
* [[Nevus depigmentosus]]

== See also ==
* [[Chromatophore]] (the pigment [[cell type]] found in [[poikilotherm]] animals)
* [[Eye color]]
* [[Mole (skin marking)]]
* [[Tanning activator]]
* [[List of distinct cell types in the adult human body]]
* [[List of human cell types derived from the germ layers]]

== References ==
{{Reflist|30em}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Ito S | title = The IFPCS presidential lecture: a chemist's view of melanogenesis | journal = Pigment Cell Research | volume = 16 | issue = 3 | pages = 230–6 | date = June 2003 | pmid = 12753395 | doi = 10.1034/j.1600-0749.2003.00037.x }}
* {{cite journal | vauthors = Millington GW | title = Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors | journal = Clinical and Experimental Dermatology | volume = 31 | issue = 3 | pages = 407–12 | date = May 2006 | pmid = 16681590 | doi = 10.1111/j.1365-2230.2006.02128.x | s2cid = 25213876 }}
{{refend}}

==External links==
{{Commons category|Melanocytes}}
* {{BUHistology|07903loa}} - "Eye: fovea, RPE"
* {{BUHistology|08103loa}} - "Integument: pigmented skin"

{{Authority control}}

[[Category:Human cells]]
[[Category:Pigment cells]]
[[Category:Skin anatomy]]
[[Category:Epithelial cells]]