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Multimodal analyses of vitiligo skin idenitfy tissue characteristics of stable disease
Jessica Shiu, … , Mihaela Balu, Anand K. Ganesan
Jessica Shiu, … , Mihaela Balu, Anand K. Ganesan
Published June 2, 2022
Citation Information: JCI Insight. 2022;7(13):e154585. https://doi.org/10.1172/jci.insight.154585.
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Research Article Dermatology

Multimodal analyses of vitiligo skin idenitfy tissue characteristics of stable disease

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Abstract

Vitiligo is an autoimmune skin disease characterized by the destruction of melanocytes by autoreactive CD8+ T cells. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells, but the persistence of white patches in stable disease is poorly understood. The interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools. We combine noninvasive multiphoton microscopy (MPM) imaging and single-cell RNA-Seq (scRNA-Seq) to identify subpopulations of keratinocytes in stable vitiligo patients. We show that, compared with nonlesional skin, some keratinocyte subpopulations are enriched in lesional vitiligo skin and shift their energy utilization toward oxidative phosphorylation. Systematic investigation of cell-to-cell communication networks show that this small population of keratinocyte secrete CXCL9 and CXCL10 to potentially drive vitiligo persistence. Pseudotemporal dynamics analyses predict an alternative differentiation trajectory that generates this new population of keratinocytes in vitiligo skin. Further MPM imaging of patients undergoing punch grafting treatment showed that keratinocytes favoring oxidative phosphorylation persist in nonresponders but normalize in responders. In summary, we couple advanced imaging with transcriptomics and bioinformatics to discover cell-to-cell communication networks and keratinocyte cell states that can perpetuate inflammation and prevent repigmentation.

Authors

Jessica Shiu, Lihua Zhang, Griffin Lentsch, Jessica L. Flesher, Suoqin Jin, Christopher Polleys, Seong Jin Jo, Craig Mizzoni, Pezhman Mobasher, Jasmine Kwan, Francisca Rius-Diaz, Bruce J. Tromberg, Irene Georgakoudi, Qing Nie, Mihaela Balu, Anand K. Ganesan

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Figure 6

Cell-to-cell communication analysis reveals major signaling changes between nonlesional and lesional vitiligo skin.

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Cell-to-cell communication analysis reveals major signaling changes betw...
(A) Number of inferred interactions among all cell subpopulations between nonlesional (NL) and lesional (LS) skin. (B) The relative information flow of all significant signaling pathways within the inferred networks between nonlesional and lesional skin. Signaling pathways labeled in green represent pathways enriched in nonlesional skin, the middle ones colored by black are equally enriched in both nonlesional and lesional skin, and the ones colored by purple are more enriched in lesional skin. (C) Visualization of outgoing and incoming interaction strength of each cell subpopulation in the inferred cell-to-cell communication network of nonlesional (top) and lesional skin (bottom). The dot sizes are proportional to the number of total interactions associated with each cell subpopulation. Dashed circle indicates the most altered cell subpopulations when comparing the outgoing and incoming interaction strength between nonlesional and lesional skin. (D) The signaling changes associated with the 3 most altered cell subpopulations.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

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