SkinChronicles, No 2, November 2024, by Alessia Paganelli

While the primary focus of vitiligo research has traditionally been on melanocytes, this article explored the involvement of dermal fibroblasts in vitiligo and highlighted their impact on skin health, even in areas that appear clinically unaffected.

One of the central observations is that fibroblasts in vitiligo exhibit signs of oxidative stress and undergo morphological changes associated with a myofibroblast phenotype. This transformation seems to be driven by elevated levels of reactive oxygen species (ROS), potentially due to intrinsic mitochondrial dysfunction. These oxidative conditions, along with the involvement of specific cytokines such as IL-6, appear to promote myofibroblast differentiation independently of the classical mediator transforming growth factor-β, suggesting a complex interplay of factors contributing to fibroblast alteration in vitiligo.

Additionally, vitiligo fibroblasts (lesional and non-lesional) seem to possess features characteristic of premature senescence. This stress-induced senescence is further marked by increased levels of cholesterol and oxysterols, hinting at a broader cellular imbalance within the dermal compartment and pointing to a skin-wide disruption beyond just depigmented areas typically associated with vitiligo.

Another significant observation is the impact of fibroblasts on melanocyte functionality. Vitiligo-affected fibroblasts release a variety of bioactive factors like hepatocyte growth factor (HGF) and Dickkopf1 (DKK1), inducing downregulation of E-cadherin in melanocytes. This disruption in E-cadherin expression can impair melanocyte adhesion to keratinocytes, making melanocytes more vulnerable to loss and/or migration to the dermis.

The research suggests that changes in oxidative stress, myofibroblast phenotypes, and cell adhesion are present even in normally pigmented skin. This widespread dermal involvement may promote melanocyte dysfunction and senescence prior to the clinical onset of visible depigmented lesions.

IMPORTANCE to the field:

These findings indicate that both oxidative stress and a senescence-prone phenotype in fibroblasts may play crucial roles in vitiligo pathogenesis, highlighting the importance of considering the entire skin, even in areas without visible lesions.

IMPORTANCE to my research:

Due to my interest in immune-mediated skin diseases and the recent therapeutic advances in the field of vitiligo, I am currently focusing my research activity on this setting. This paper paves the way for further studies on vitiligo pathogenesis, with particular interest for factors other than melanocytes and lymphocytes.