Recent advances in understanding vitiligo [version 1; referees: 3 approved]
Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be trigg...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2016-09-01
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| Series: | F1000Research |
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| Online Access: | http://f1000research.com/articles/5-2234/v1 |
| _version_ | 1818294918839271424 |
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| author | Prashiela Manga Nada Elbuluk Seth J. Orlow |
| author_facet | Prashiela Manga Nada Elbuluk Seth J. Orlow |
| author_sort | Prashiela Manga |
| collection | DOAJ |
| description | Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies. |
| first_indexed | 2024-12-13T03:39:23Z |
| format | Article |
| id | doaj.art-95d19ee336f342c593d1425e116089a5 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-13T03:39:23Z |
| publishDate | 2016-09-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-95d19ee336f342c593d1425e116089a52022-12-22T00:00:59ZengF1000 Research LtdF1000Research2046-14022016-09-01510.12688/f1000research.8976.19656Recent advances in understanding vitiligo [version 1; referees: 3 approved]Prashiela Manga0Nada Elbuluk1Seth J. Orlow2The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, 10016, USAThe Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, 10016, USAThe Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, 10016, USAVitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.http://f1000research.com/articles/5-2234/v1Antigen Processing & RecognitionAutoimmunityCellular Death & Stress ResponsesDermatologic PathologyDermatologic PharmacologyGenetics of the Immune SystemHair DiseasesImmunopharmacology & Hematologic PharmacologyInnate ImmunityLeukocyte Signaling & Gene ExpressionMedical GeneticsPhotodermatology & Skin AgingPigmentary Disorders |
| spellingShingle | Prashiela Manga Nada Elbuluk Seth J. Orlow Recent advances in understanding vitiligo [version 1; referees: 3 approved] F1000Research Antigen Processing & Recognition Autoimmunity Cellular Death & Stress Responses Dermatologic Pathology Dermatologic Pharmacology Genetics of the Immune System Hair Diseases Immunopharmacology & Hematologic Pharmacology Innate Immunity Leukocyte Signaling & Gene Expression Medical Genetics Photodermatology & Skin Aging Pigmentary Disorders |
| title | Recent advances in understanding vitiligo [version 1; referees: 3 approved] |
| title_full | Recent advances in understanding vitiligo [version 1; referees: 3 approved] |
| title_fullStr | Recent advances in understanding vitiligo [version 1; referees: 3 approved] |
| title_full_unstemmed | Recent advances in understanding vitiligo [version 1; referees: 3 approved] |
| title_short | Recent advances in understanding vitiligo [version 1; referees: 3 approved] |
| title_sort | recent advances in understanding vitiligo version 1 referees 3 approved |
| topic | Antigen Processing & Recognition Autoimmunity Cellular Death & Stress Responses Dermatologic Pathology Dermatologic Pharmacology Genetics of the Immune System Hair Diseases Immunopharmacology & Hematologic Pharmacology Innate Immunity Leukocyte Signaling & Gene Expression Medical Genetics Photodermatology & Skin Aging Pigmentary Disorders |
| url | http://f1000research.com/articles/5-2234/v1 |
| work_keys_str_mv | AT prashielamanga recentadvancesinunderstandingvitiligoversion1referees3approved AT nadaelbuluk recentadvancesinunderstandingvitiligoversion1referees3approved AT sethjorlow recentadvancesinunderstandingvitiligoversion1referees3approved |