Vitiligo is an autoimmune disease characterized by epidermal melanocyte destruction, with abnormal autoimmune responses and excessive oxidative stress as two cardinal mechanisms. Human umbilical mesenchymal stem cells‐derived exosomes (hUMSCs‐Exos) are regarded as promising therapeutic choice for autoimmune diseases due to potent immunosuppressive and anti‐oxidative properties, which can be potentiated under 3D cell culture condition. Nevertheless, whether exosomes derived from 3D spheroids of hUMSCs (3D‐Exos) exhibit considerable therapeutic effect on vitiligo and the underlying mechanism remain elusive. In this study, systemic administration of 3D‐Exos showed a remarkable effect in treating mice with vitiligo, as revealed by ameliorated skin depigmentation, less CD8⁺T cells infiltration, and expanded Treg cells in skin, and 3D‐Exos exerted a better effect than 2D‐Exos. Mechanistically, 3D‐Exos can prominently facilitate the expansion of Treg cells in vitiligo lesion and suppress H₂O₂‐induced melanocytes apoptosis. Forward miRNA profile analysis and molecular experiments have demonstrated that miR‐132‐3p and miR‐125b‐5p enriched in 3D‐Exos greatly contributed to these biological effects by targeting Sirt1 and Bak1 respectively. In aggregate, 3D‐Exos can efficiently ameliorate vitiligo by simultaneously potentiating Treg cells‐mediated immunosuppression and suppressing oxidative stress‐induced melanocyte damage via the delivery of miR‐132‐3p and miR‐125b‐5p. The employment of 3D‐Exos will be a promising treament for vitiligo.

Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.

In vitiligo, cutaneous depigmentation is accompanied by increased T cell cytolytic activity targeting melanocytes, indicating that autoimmune tolerance is disrupted. The inhibited amount and function of Tregs have been indicated to be involved in the autoimmune intolerance in vitiligo, however, with the conclusion still controversial and the involved mechanism unknown. In this study, we explored the molecular and cellular alterations accounting for the impaired Treg response in vitiligo. Our results showed that the amount of Tregs was drastically reduced in peripheral blood of active vitiligo patients. Furthermore, the immunoregulatory function of Tregs was attenuated, with lower expression of CTLA4, IL‐10 and TGF‐β. Moreover, the expression of HO‐1, a functional modulator of Tregs, was decreased in vitiligo Tregs, and the concentrations of HO‐1 metabolites, including bilirubin, CoHb and iron, were correspondingly decreased in serum of vitiligo patients. In addition, we treated the Tregs from vitiligo patients with Hemin, an agonist of HO‐1, and found that enhanced HO‐1 expression restored the function of Tregs by up‐regulating IL‐10 expression. Our study demonstrates the essential role of HO‐1 in the impaired Treg response in vitiligo and indicates the potential of HO‐1 as a therapeutic target in vitiligo management.