Understanding the pathogenesis of vitiligo is critical for improving treatment options for patients. Despite affecting 1-2% of the world’s population, however, a definitive understanding of the mechanism(s) underpinning vitiligo has proven elusive. Universal to existing theories for vitiligo is that pigment producing cells called melanocytes, are damaged, which in their review, Wu et al. (2021) state is the most notable feature of the disorder.
The authors aim to summarise the latest insights by delving into established forms of melanocyte death in vitiligo (including apoptosis, necrosis, and autophagy), and new forms of regulated cell death discovered in recent years, namely necroptosis, pyroptosis, ferroptosis, anoikis and phagoptosis (see glossary below).
Historically, apoptosis was considered the primary form of melanocyte death in vitiligo. However, more recent research shows evidence pointing to the contrary. Inflammatory cells in vitiliginous lesions, in addition to variance in the shape and biomarkers of dead melanocytes, suggest non‐apoptotic forms of regulated cell death are involved.
The more recently recognised forms of cell death have been found to play significant roles in several diseases. For example, ferroptosis is induced by oxidative stress. In ischaemic stroke, the use of ferroptosis inhibitors has been found to improve the recovery rate of patients (as noted by Li et al. (2020) in an article published in the journal Cell Death & Disease). In another example, necroptosis, a programmed inflammatory cell death pathway, plays a key role in promoting inflammation in inflammatory bowel disease (IBD) and inflammatory skin diseases, as well as establishing tumour immunotolerance in some cancers, according to a 2018 article by Najafov et al. in Cancer Trends.
While Wu et al. outline some of the new work shedding light on the disease, more research is needed to better understand the mechanism(s) of action of vitiligo leading to cell death and depigmentation.
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Glossary – see full review by Wu et al. (2021) for in-depth descriptions.
|APOPTOSIS||A form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area. Vital for normal growth in multicellular organisms.|
|AUTOPHAGY||A highly conserved catabolic process induced under cellular stress by degrading damaged organelles and proteins through a lysosome‐dependent degradation process.|
|NECROSIS||A type of uncontrolled cell death that can occur in response to various stimuli, such as infection, toxins, chemicals, or injury.|
|ANOIKIS||A distinctive type of apoptosis provoked specifically by loss of anchorage.|
|FERROPTOSIS||A form of regulated cell death, characterised by increased level of iron and initial lipid peroxidation without the activation of caspases.|
|NECROPTOSIS||A regulated form of necrotic cell death, triggered by members of the TNF family, Toll‐like receptors, DNA and/or RNA sensors through a different mechanism dependent on inhibition of caspase‐8.|
|PHAGOPTOSIS||Also known as primary phagocytosis. The reversible exposure of “eat‐me” signals, and/or the loss of “don’t‐eat‐me” signals on the surface of a viable cell lead to phagoptosis.|
|PYROPTOSIS||A highly inflammatory form of necrotic cell death regulated mainly by caspase‐1, which is initiated following large supramolecular complex termed inflammasome activation.|