Project Title: Elucidating the Role of Keratinocyte Metabolism in Vitiligo Persistence
Vitiligo is an autoimmune skin disease characterized by the progressive destruction of melanocytes by autoreactive T cells, resulting in disfiguring white patches that negatively affects patients’ quality of life. While the role of the immune system is well defined in disease initiation, factors that drive vitiligo persistence are unknown. In particular, it is not understood why in the absence of active CD8 + T cell-mediated killing, white patches persist. We recently used multiphoton microscopy (MPM) to visualize NADH intrinsic two-photon excited fluorescence in patient-matched vitiligo and nonlesional skin and found that keratinocyte metabolism is altered in disease skin. In parallel, we used single cell transcriptomics to identify unique populations of keratinocytes present in stable vitiligo skin. Compared to patient-matched nonlesional skin, there was an enrichment of a unique population of keratinocytes that exhibited increased expression of keratins associated with cell stress (KRT6B) and chemokines known to induce vitiligo (CXCL9, CXCL10), implicating a role for these cells in disease persistence. Based on these observations, we hypothesize that a unique population of stressed keratinocytes drives vitiligo disease persistence, either through their continued recruitment of immune cells to diseased skin or through inhibiting melanocyte migration.