Autoimmune etiology of generalized vitiligo.
Vitiligo is characterized by progressive skin depigmentation resulting from an autoimmune response targeting epidermal melanocytes. Melanocytes are particularly immunogenic by virtue of the contents of their melanosomes, generating the complex radical scavenging molecule melanin in a process that involves melanogenic enzymes and structural components, including tyrosinase, MART-1, gp100, TRP-2 and TRP-1. These molecules are also prime targets of the immune response in both vitiligo and melanoma. The immunogenicity of melanosomal proteins can partly be explained by the dual role of melanosomes, involved both in melanin synthesis and processing of exogenous antigens. Melanocytes are capable of presenting antigens in the context of MHC class II, providing HLA-DR+ melanocytes in perilesional vitiligo skin the option of presenting melanosomal antigens in response to trauma and local inflammation. Type I cytokine-mediated immunity to melanocytes in vitiligo involves T cells reactive with melanosomal antigens, similar to T cells observed in melanoma. In vitiligo, however, T cell tuning allows T cells with higher affinity for melanocyte differentiation antigens to enter the circulation after escaping clonal deletion in primary lymphoid organs. The resulting efficacious and progressive autoimmune response to melanocytes provides a roadmap for melanoma therapy.
Le Poole
I Caroline
IC
Department of Pathology, Oncology Institute, Loyola University, Chicago, IL, USA. ilepool@lumc.edu
Luiten
Rosalie M
RM
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D017637:Clonal Deletion; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000276:immunology; D058965:MART-1 Antigen; D008543:Melanins / Q000276:immunology; D020460:Melanosomes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D010088:Oxidoreductases / Q000276:immunology; D010858:Pigmentation / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D014820:Vitiligo / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D001324:Autoantigens; D006684:HLA-DR Antigens; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008543:Melanins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase