An Luye, Kim Dahihm, Donahue Leanne R, Mejooli Menansili Abraham, Eom Chi-Yong, Nishimura Nozomi, White Andrew C
Department of Biomedical Sciences, Cornell University, Ithaca, NY, 14850, USA.
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14850, USA.
Nat Commun. 2024 Jan 27;15(1):796. doi: 10.1038/s41467-024-45034-3.
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.
白癜风是一种由皮肤黑素细胞缺失引起的自身免疫性皮肤病。尽管光疗和T细胞抑制疗法已被广泛用于诱导表皮重新色素沉着，但由于我们对控制这一过程的细胞和分子机制了解不足，很少能实现完全色素沉着恢复。在这里，我们确定了雄性和雌性小鼠之间独特的黑素细胞干细胞（McSC）表皮迁移率，这是由于紫外线B照射产生的性别差异皮肤炎症反应所致。使用基因工程小鼠模型以及无偏向的大量和单细胞mRNA测序方法，我们确定通过环氧化酶及其下游前列腺素产物来调节炎症反应，可调控McSC增殖以及对紫外线B照射的表皮迁移。此外，我们证明一种同时操纵巨噬细胞和T细胞（即先天免疫和适应性免疫）的联合疗法可显著促进表皮黑素细胞再填充。基于这些发现，我们提出了一种针对白癜风等色素脱失病症患者色素再生的新型治疗策略。
