Autoimmune diseases

Keratinocyte metabolism may be key to repigmentation in stable vitiligo

New vitiligo research has revealed mechanisms related to cell-cell communication networks and keratinocyte cell state that may perpetuate inflammation and prevent repigmentation in stable disease.

Scientists at the University of California, Irvine, (UCI) say melanocyte destruction in active vitiligo is know to be mediated by CD8+ T cells, but until now, it has not been well understood why the white patches in stable disease persist.

There was a need to investigate when and why metabolically altered keratinocytes first appear and how they may affect the repigmentation process in patients undergoing treatment, they suggested.

They therefore used advanced imaging with transcriptomics and bioinformatics to investigate the interactions between keratinocytes, immune cells and melanocytes in vitiligo.

They combined non-invasive multiphoton microscopy (MPM) imaging and single-cell RNA sequencing (scRNA-seq) to identify subpopulations of keratinocytes in stable vitiligo patients.

They found that compared to normal skin, the keratinocytes in stable vitiligo patients were enhanced and showed a shift in energy utilisation towards oxidative phosphorylation.

Further investigation of cell-cell communication networks showed that this population of keratinocyte secreted the chemokines CXCL9 and CXCL10 to potentially drive vitiligo persistence.

These chemokines have previously been shown to bind to receptors that regulate immune responses by recruiting and activating T cells, monocytes, and also natural killer cells.

Further imaging of vitiligo patients undergoing punch grafting treatment showed that the keratinocytes favouring oxidative phosphorylation persist in non-responders. But in patients that responded to punch grafting treatment, these changes were reversed, highlighting their role in disease persistence, the researchers said

The findings raised the possibility of targeting keratinocyte metabolism in vitiligo treatment, they suggested, although further studies are needed to improve the understanding of how keratinocyte states affect the tissue microenvironment and contribute to disease pathogenesis.

“This discovery will enable us to determine why white patches continue to persist in stable vitiligo disease, which could lead to new therapeutics to treat this disease, “said study co-authors Dr Anand K. Ganesan, professor of dermatology and vice chair for dermatology research at UCI School of Medicine

The study is published in JCI Insight.


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