Autophagy regulates cellular turnover by disassembling unnecessary or dysfunctional constituents. Recent studies demonstrated that autophagy and its regulators play a wide variety of roles in melanocyte biology. Activation of autophagy is known to induce melanogenesis and regulate melanosome biogenesis in melanocytes. Also, autophagy induction was reported to regulate physiologic skin color via melanosome degradation, although the downstream effectors are not yet clarified. To determine the role of autophagy as a melanosome degradation machinery, we administered several autophagy inducers in human keratinocytes and melanocytes. Our results showed that the synthetic autophagy inducer PTPD‐12 stimulated autophagic flux in human melanocytes and in keratinocytes containing transferred melanosomes. Increased autophagic flux led to melanosome degradation without affecting the expression of MITF. Furthermore, the color of cell pellets of both melanocytes and keratinocytes was visibly lightened. Inhibition of autophagic flux by chloroquine resulted in marked attenuation of PTPD‐12‐induced melanosome degradation, whereas the expression of melanogenesis pathway genes and proteins remained unaffected. Taken together, our results suggest that the modulation of autophagy can contribute to the regulation of melanocyte biology and skin pigmentation.

Extracellular adenosine 5ʹ-triphosphate (ATP) is a well-known inflammasome-activating signal. Emerging evidence demonstrates a critical role for inflammasome activation in vitiligo pathogenesis. However, the specific molecular mechanism of inflammasome-dependent melanocyte degeneration in vitiligo is still not clear. This study presents how extracellular ATP, released from keratinocytes by oxidative stress, affects melanocyte survival in vitiligo skin. H 2 O 2-induced oxidative injury increased ATP release from keratinocytes and skin tissues. The high concentration of extracellular ATP induced both ROS production and cell death in melanocytes. Treatment with ATP caused the activation of caspase-1 as well as the production of active forms of IL-1b and IL-18 via P2X7 receptor in keratinocytes and melanocytes. Lesional and perilesional skin of vitiligo showed higher levels of ATP as well as upregulation of active caspase-1 compared with nonlesional skin, suggesting its possible role in inflammasome activation in vitiligo. Moreover, the elevated expression of CXCL9 in keratinocytes, mediated through ATP/P2X7 receptoredependent inflammasome activation, was responsible for CLA þ CD8 þ Tcell chemotaxis into the skin. These results demonstrate that extracellular ATP as a danger signal activates the inflammasome pathway and increases cutaneous chemotaxis of CD8 þ T cells via CXCL9 in vitiligo. Therefore, targeting ATP-P2X7 signaling may be a potential strategy for vitiligo treatment.

Background Extrinsic skin aging caused by atmospheric pollutants is associated with a sustained inflammatory response which is a significant risk factor for lentigines and melasma. Aims The aim of this study was to evaluate the efficacy of topical application of combination formulation of vitamin C, vitamin E, and ferulic acid as an adjuvant to Q‐switched Nd:YAG (QSNY) lasers treatment in individuals with lentigines and melasma. Methods A single blinded, prospective, randomized split‐face trial was conducted. Eighteen men and women between 26 and 53 years old were treated with a combination antioxidant serum on one randomized side of their face immediately after QSNY laser and twice daily for 2 weeks. Patients were evaluated using digital photography and spectrometry to assess the melanin index and erythema index. Melasma severity score and global improvement scores also were assessed. Results The treated side of the face exhibited a significantly greater reduction in the melanin index. There was no significant difference in post‐treatment erythema. More clinical improvement was observed on the treated side compared with the untreated side. Conclusions Our study suggests that topical application of a combination vitamins C, E, and ferulic acid antioxidant formula may be effective as an adjuvant option in QSNY lasers.