Innate immune mechanisms in vitiligo: danger from within

• Melanocytes from vitiligo patients display features of elevated cellular stress.
• Stressed cells produce damage-associated molecular patterns (DAMPs).
• DAMPs activate innate immune cell populations through pattern recognition receptors.
• Activated innate immune cells can promote adaptive immunity in vitiligo.
• Activated stress pathways appear to play a role in organ-specific autoimmunity.

Vitiligo is an autoimmune disease of the skin in which melanocytes are destroyed by antigen-specific T cells, resulting in patchy depigmentation. Although adaptive immunity plays a clear role in disease progression, initiating factors are largely unknown. Many studies report that cellular stress pathways are dysregulated in melanocytes from vitiligo patients, suggesting that melanocyte-intrinsic defects participate in disease pathogenesis. Recent studies reveal that melanocyte stress generates damage-associated molecular patterns that activate innate immunity, thus connecting stress to organ-specific inflammation. Genetic studies in vitiligo support a role for stress, innate immunity, and adaptive mechanisms. Here, we discuss advances in the field that highlight how cellular stress, endogenous danger signals, and innate immune activation promote the onset of vitiligo.