Abstract
Multiple factors are involved in the process leading to melanocyte loss in vitiligo including environmental triggers, genetic polymorphisms, metabolic alterations, and autoimmunity. This review aims to highlight current knowledge on how danger signals released by stressed epidermal cells in a predisposed patient can trigger the innate immune system and initiate a cascade of events leading to an autoreactive immune response, ultimately contributing to melanocyte disappearance in vitiligo. We will explore the genetic data available, the specific role of damage-associated-molecular patterns, and pattern-recognition receptors, as well as the cellular players involved in the innate immune response. Finally, the relevance of therapeutic strategies targeting this pathway to improve this inflammatory and autoimmune condition is also discussed.
Highlights
Clinical, translational, and fundamental research studies performed over the last decade have tremendously improved our understanding of vitiligo physiopathology and new therapeutic perspectives are emerging for this disease which suffers from the lack of effective treatments
This short review is focusing on the innate side of the disease, discussing how genetic and transcriptomic data revealed the importance of innate immunity in vitiligo, as well as the interplay between epidermal cells and innate immune cells to contribute to the initiation and/or progression of the disease through the release of danger signals, cytokines, and chemokines, leading to activation of the adaptive immune response and the loss of Innate Immunity and Vitiligo melanocyte
These data illustrate that vitiligo patients have genetic predisposition affecting their innate immune response in their apparent non-affected skin. Such findings may be indicative of a subclinical activation of innate immunity, loss of protective mechanisms to stress, and/or increased sensitivity to endogenous or external stress, such as several damage-associated-molecular patterns (DAMPs) or pathogen-associated-molecular patterns (PAMPs) [12]
Summary
Translational, and fundamental research studies performed over the last decade have tremendously improved our understanding of vitiligo physiopathology and new therapeutic perspectives are emerging for this disease which suffers from the lack of effective treatments. Besides the role of the adaptive immune response, increasing data highlight a major role of innate immune cell subsets and their immunerelated pathways that could spark the induction of the disease in the “normal-appearing” skin. This short review is focusing on the innate side of the disease, discussing how genetic and transcriptomic data revealed the importance of innate immunity in vitiligo, as well as the interplay between epidermal cells (keratinocytes and melanocytes) and innate immune cells to contribute to the initiation and/or progression of the disease through the release of danger signals, cytokines, and chemokines, leading to activation of the adaptive immune response and the loss of. This better understanding offers novel insight into the development of targeted therapies that could prevent the induction as well as the recurrence of the disease
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