黑色素干细胞的性别二态性揭示皮肤复色联合治疗策略

中文摘要：

白斑病（Vitiligo）是一种由皮肤黑素细胞缺失引起的自身免疫性皮肤病。虽然光疗和T细胞抑制疗法已被广泛用于诱导表皮色素再生，但由于人们对这一过程的细胞和分子调控机制理解不足，很少能实现色素恢复。本研究发现，雌雄小鼠黑色素干细胞（McSC）的表皮迁移速率存在显著差异，这种差异源于紫外线B照射引发的性别二态性皮肤炎症反应。通过使用基因工程小鼠模型及无偏倚的批量mRNA测序与单细胞mRNA测序技术，我们证实通过调控环氧合酶及其下游前列腺素产物的炎症反应，可以有效调节紫外线B暴露下黑色素干细胞的增殖和表皮迁移。进一步研究表明，通过联合调控巨噬细胞和T细胞（即先天免疫和适应性免疫）的疗法可显著促进表皮黑素细胞再生。基于这些发现，我们提出了一种针对Vitiligo等色素脱失性疾病患者的新型复色治疗策略。

英文摘要：

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.

论文信息：

论文题目：Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for

cutaneous repigmentation

期刊名称：Nature Communications

时间期卷：15, Article number: 796 (2024)

在线时间：2024年1月27日

DOI：doi.org/10.1038/s41467-024-45034-3

产品信息：

货号：CP-005-005

规格：5ml+5ml

品牌：Liposoma

产地：荷兰

名称：Clodronate Liposomes and Control Liposomes

办事处：Target Technology（靶点科技）

白斑病是由于皮肤黑素细胞被破坏，引发皮肤黑色素缺乏，形成局部白斑的疾病。其病因可能与自身免疫系统疾病、遗传、神经化学物质等因素有关，不同年龄、性别和种族的人都可能患病。皮肤色素障碍疾病种类繁多。白斑病作为一种典型的自身免疫性疾病，全球发病率达0.5%-2%，其特征表现为表皮黑素细胞缺失导致的色素脱失斑块。

白斑病发病机制涉及遗传易感性、氧化应激、先天/适应性免疫异常及环境刺激等多重因素，这些因素共同导致CD8⁺T细胞异常活化，最终引发表皮黑素细胞破坏。因此，针对T细胞的靶向治疗成为研究焦点。近期FDA批准的多种JAK抑制剂通过抑制CD8⁺T细胞募集，在改善白斑病患者复色方面显示出疗效。尽管II/III期临床试验证实这些疗法可显著改善皮肤色素沉着，但患者应答存在个体差异，且鲜有实现持久的色素再生。

氯膦酸盐二钠脂质体清除单核巨噬细胞，在白斑病模型中单核巨噬细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：

Clodronate liposome treatment

Mice were given doxycycline in water and the first dose of clodronate liposomes (CL) or PBS liposomes (PL) (Liposoma, Cat#CP-005-005) on the day prior to the first UVB irradiation. Male and female mice were given 250 µl and 200 µl CL/PL, respectively, due to weight differences. From one day after the first UVB, mice were given CL/PL daily until the collection day or 2 days following the third UVB. Mice for McSC translocation analysis were collected seven days following the third UVB irradiation.