Editing Melanocyte (section)

== 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>