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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 cells including: branched morphology; phagocytic capabilities; and presentation of antigens to T-cells; production and release of cytokines. Although melanocytes are dendritic in form and share many characteristics with dendritic cells such as Langerhans cells, they originate from neural crest cells rather than hematopoietic stem cells in the bone marrow. As such, although morphologically and functionally similar, melanocytes and dendritic cells are not the same.

Melanocytes express MHC Class II, a type of MHC expressed only by certain antigen presenting cells of the immune system. All cells in any given vertebrate express MHC, but most cells only express MHC class I. The other class of MHC, Class II, is found only on "professional" antigen presenting cells such as dendritic cells, macrophages, B cells, and melanocytes. Importantly, melanocytes stimulated by cytokines express surface proteins such as CD40 and ICAM1 in addition to MHC class II, allowing for co-stimulation of T cells.

In addition to presenting antigen, one of the primary roles of melanocytes in the immune response is cytokine production. Melanocytes express many proinflamatory cytokines including IL-1, IL-3, IL-6, IL-8, TNF-α, and TGF-β Like other immune cells, melanocytes secrete these cytokines in response to activation of Pattern Recognition Receptors (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 epidermis to be sentinels against harmful pathogens. Melanocytes reside in the stratum basale, the lowest layer of the epidermis, 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 keratinocytes and Langerhans cells, both of which are also actively phagocytic, to contribute to the immune response.