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Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation

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Listed:
  • Luye An

    (Cornell University)

  • Dahihm Kim

    (Cornell University)

  • Leanne R. Donahue

    (Cornell University)

  • Menansili Abraham Mejooli

    (Cornell University)

  • Chi-Yong Eom

    (Cornell University)

  • Nozomi Nishimura

    (Cornell University)

  • Andrew C. White

    (Cornell University)

Abstract

Vitiligo is an autoimmune skin disease caused by cutaneous melanocyte loss. Although phototherapy and T cell suppression therapy have been widely used to induce epidermal re-pigmentation, full pigmentation recovery is rarely achieved due to our poor understanding of the cellular and molecular mechanisms governing this process. Here, we identify unique melanocyte stem cell (McSC) epidermal migration rates between male and female mice, which is due to sexually dimorphic cutaneous inflammatory responses generated by ultra-violet B exposure. Using genetically engineered mouse models, and unbiased bulk and single-cell mRNA sequencing approaches, we determine that manipulating the inflammatory response through cyclooxygenase and its downstream prostaglandin product regulates McSC proliferation and epidermal migration in response to UVB exposure. Furthermore, we demonstrate that a combinational therapy that manipulates both macrophages and T cells (or innate and adaptive immunity) significantly promotes epidermal melanocyte re-population. With these findings, we propose a novel therapeutic strategy for repigmentation in patients with depigmentation conditions such as vitiligo.

Suggested Citation

  • Luye An & Dahihm Kim & Leanne R. Donahue & Menansili Abraham Mejooli & Chi-Yong Eom & Nozomi Nishimura & Andrew C. White, 2024. "Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45034-3
    DOI: 10.1038/s41467-024-45034-3
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