Stable vitiligo skin lesions have a distinct cellular makeup compared to active vitiligo melanocytes due to their unique genetic signatures and metabolic profiles, causing proinflammatory responses and a “stressed” cellular state.
- Stable vitiligo lesions have cellular profiles that are distinct from those of active vitiligo melanocytes.
- Keratinocytes in depigmented lesions have distinct genetic signatures and metabolic profiles.
- “Stressed” keratinocytes contribute to proinflammatory responses in stable vitiligo.
Vitiligo is a complex autoimmune skin condition that is characterized by the progressive destruction of melanocytes by autoreactive CD8+ T cells. Vitiligo is chronic and progressive, but some patients reach a state of stability whereby their lesions stop spreading and no new lesions emerge. Most research seeks to understand the active disease state, but stable vitiligo may have a unique cellular profile and dynamics.
Noninvasive Imaging Technique Enables Observation of Cellular Metabolism
A recent study published in JCI Insight used a noninvasive imaging technique, multiphoton microscopy, to observe keratinocyte metabolism in stable vitiligo patients. This technique, validated in healthy human skin, allows for the visualization of cellular metabolism by assessing mitochondrial clustering changes in response to metabolic activities like glycolysis, oxidative phosphorylation, and fatty acid oxidation and synthesis, which have been difficult to assess in vitiligo-lesioned skin.
Altered Mitochondrial Clustering in Lesioned Skin
Researchers found that lesioned skin had less altered mitochondrial clustering compared to that of non-lesioned skin, indicating changes in keratinocyte metabolism. Normally, changes in metabolic activity can be seen in different layers of the epidermis, but this differentiation was lost in lesioned skin areas. Keratinocytes from lesions had distinct genetic signatures resembling a “stressed” state, enriched with inflammatory biomarkers and immunoregulators. Even in stable vitiligo lesions, cells still have active inflammatory profiles and communicate with immune cells.
Importance of Tracking Cellular Dynamics in Vitiligo Patients
Characterizing skin cell states in vitiligo can be challenging, but noninvasive imaging techniques and single-cell analyses have begun to uncover the cellular dynamics affected in lesioned patient skin. Researchers have recently identified a unique subpopulation of metabolically compromised “stressed” keratinocytes in patients with stable pigmentation. Tracking such changes in cellular dynamics in vitiligo patients will be important for determining the best course of treatment.
Shiu, J., Zhang, L., Lentsch, G., Flesher, J. L., Jin, S., Polleys, C., Jo, S. J., Mizzoni, C., Mobasher, P., Kwan, J., Rius-Diaz, F., Tromberg, B. J., Georgakoudi, I., Nie, Q., Balu, M., & Ganesan, A. K. (2022). Multimodal analyses of vitiligo skin identify tissue characteristics of stable disease. JCI Insight, 7(13). https://doi.org/10.1172/jci.insight.154585