Non‐invasive optical biopsy by multiphoton microscopy identifies the live morphology of common melanocytic nevi

Lentsch, Griffin; Valdebran, Manuel; Saknīte, Inga; Smith, Janellen; Linden, Kenneth G.; König, Karsten; Barr, Ronald J.; Harris, Ronald M.; Tromberg, Bruce J.; Ganesan, Anand K.; Zachary, Christopher B.; Kelly, Kristen M.; Balu, Mihaela

doi:10.1111/pcmr.12902

Cited by 14 publications

(10 citation statements)

References 19 publications

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“…Whether these drugs will also inhibit keratinocyte-derived signals that affect immune cell and melanocyte recruitment is unclear and represent an unexplored area for drug targeting in vitiligo. Interestingly, stress keratinocytes expressing KRT6 , 16 and S100A8/9 have been identified in the human epidermis of psoriasis and melanomas, raising the possibility that they can play a wide variety of roles in the diseased skin tissue microenvironment ( 52 – 54 ). Further studies on stress keratinocytes will improve our understanding how keratinocyte states affect the tissue microenvironment and contribute to disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Multimodal Analyses of Stable Vitiligo Skin Identify Tissue Interactions That Control Disease Persistence

Shiu

Zhang

Lentsch

et al. 2021

Preprint

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Vitiligo is an autoimmune skin disease that is characterized by the progressive destruction of melanocytes by autoreactive CD8+ T cells. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells but why white patches in stable disease persist 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. Here, we combine non-invasive multiphoton microscopy (MPM) imaging and single-cell RNA sequencing (scRNA-seq) to identify distinct subpopulations of keratinocytes in lesional skin of stable vitiligo patients. We show that these keratinocytes are enriched in lesional vitiligo skin and differ in metabolism, an observation corroborated by both MPM and scRNA-seq. Systematic investigation of cell-cell communication show that CXCL is the prominent signaling change in this small population of keratinocytes, which secrete CXCL9 and CXCL10 to create local inflammatory cytokine loops with T cells to drive stable vitiligo persistence. Pseudotemporal dynamics analyses predict an alternative keratinocyte differentiation trajectory that generates this new population of keratinocytes in vitiligo skin. In summary, we couple advanced imaging with transcriptomics and bioinformatics to discover cellcell communication networks and keratinocyte cell states that perpetuate inflammation and prevent repigmentation.One Sentence SummaryCommunication between keratinocytes, immune cells, and melanocytes maintain depigmented patches in stable vitiligo.

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Section: Discussionmentioning

confidence: 99%

Multimodal Analyses of Stable Vitiligo Skin Identify Tissue Interactions That Control Disease Persistence

Shiu

Zhang

Lentsch

et al. 2021

Preprint

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“…AF is another endogenous source of contrast and has been popular with multiphoton microscopy. 72 , 73 However, AF is weaker than backscattered light, and can impose limits on imaging speed and field of view.…”

Section: Translational Challengesmentioning

confidence: 99%

In vivo microscopy as an adjunctive tool to guide detection, diagnosis, and treatment

et al. 2022

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“…Multiphoton microscopy (MPM) is a unique tool for this purpose and has broad applications in human skin (12)(13)(14)(15)(16)(17)(18)(19). MPM is a noninvasive imaging technique capable of providing images with submicron resolution and label-free molecular contrast, which can be used to characterize keratinocyte metabolism in human skin (20,21).…”

Section: Introductionmentioning

confidence: 99%

Multimodal analyses of vitiligo skin identifies tissue characteristics of stable disease

Shiu¹,

Zhang²,

Lentsch³

et al. 2022

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Non‐invasive optical biopsy by multiphoton microscopy identifies the live morphology of common melanocytic nevi

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 19 publications

Multimodal Analyses of Stable Vitiligo Skin Identify Tissue Interactions That Control Disease Persistence

Multimodal Analyses of Stable Vitiligo Skin Identify Tissue Interactions That Control Disease Persistence

In vivo microscopy as an adjunctive tool to guide detection, diagnosis, and treatment

Multimodal analyses of vitiligo skin identifies tissue characteristics of stable disease

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