Conclusion and Prospects
Sufficient is now understood about the pathogenesis of vitiligo to permit targeted pharmacological intervention at the appropriate immunological steps. However, the exact modus by which the genetic interacts with the environment, and with the immune system still requires considerable elucidation. What can be said is that both environmental factors and cell-intrinsic defects instigate stress responses in melanocytes, resulting in the synthesis of DAMPs that elicit innate immune cells, which in turn activate adaptive immunity that ultimately targets melanocytes. A genetic predisposition to autoimmunity may underlie inappropriate immune responses in vitiligo, but immune responses may occur secondarily as a result of melanocyte damage by other factors, as when autoantibodies have been observed directed against intracellular pigment cell proteins — exposure of cryptic epitopes and protein modification occurring during apoptosis [215]. Following processing by dendritic cells, antigenic proteins can be presented to either autoreactive T cells, which evaded clonal deletion, or to naïve T cells, which have not been tolerised against cryptic epitopes [216]. In consequence, antibodies can be secreted following autoreactive B cell stimulation by activated autoreactive CD4+ T lymphocytes [216], which may then act to further aggravate vitiligo. However, it is possible that antibodies play no part in the pathogenesis of vitiligo, but might indicate the existence of autoreactive anti-melanocyte T cells are capable of destroying melanocytes, a scenario that merits further investigation.