黑色素干細(xì)胞的性別二態(tài)性揭示皮膚復(fù)色聯(lián)合治療策略

中文摘要：

白斑病（Vitiligo）是一種由皮膚黑素細(xì)胞缺失引起的自身免疫性皮膚病。雖然光療和T細(xì)胞抑制療法已被廣泛用于誘導(dǎo)表皮色素再生，但由于人們對這一過程的細(xì)胞和分子調(diào)控機制理解不足，很少能實現(xiàn)色素恢復(fù)。本研究發(fā)現(xiàn)，雌雄小鼠黑色素干細(xì)胞（McSC）的表皮遷移速率存在顯著差異，這種差異源于紫外線B照射引發(fā)的性別二態(tài)性皮膚炎癥反應(yīng)。通過使用基因工程小鼠模型及無偏倚的批量mRNA測序與單細(xì)胞mRNA測序技術(shù)，我們證實通過調(diào)控環(huán)氧合酶及其下游前列腺素產(chǎn)物的炎癥反應(yīng)，可以有效調(diào)節(jié)紫外線B暴露下黑色素干細(xì)胞的增殖和表皮遷移。進一步研究表明，通過聯(lián)合調(diào)控巨噬細(xì)胞和T細(xì)胞（即先天免疫和適應(yīng)性免疫）的療法可顯著促進表皮黑素細(xì)胞再生。基于這些發(fā)現(xiàn)，我們提出了一種針對Vitiligo等色素脫失性疾病患者的新型復(fù)色治療策略。

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.

論文信息：

論文題目：Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for

cutaneous repigmentation

期刊名稱：Nature Communications

時間期卷：15, Article number: 796 (2024)

在線時間：2024年1月27日

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

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點科技）

白斑病是由于皮膚黑素細(xì)胞被破壞，引發(fā)皮膚黑色素缺乏，形成局部白斑的疾病。其病因可能與自身免疫系統(tǒng)疾病、遺傳、神經(jīng)化學(xué)物質(zhì)等因素有關(guān)，不同年齡、性別和種族的人都可能患病。皮膚色素障礙疾病種類繁多。白斑病作為一種典型的自身免疫性疾病，全球發(fā)病率達0.5%-2%，其特征表現(xiàn)為表皮黑素細(xì)胞缺失導(dǎo)致的色素脫失斑塊。

白斑病發(fā)病機制涉及遺傳易感性、氧化應(yīng)激、先天/適應(yīng)性免疫異常及環(huán)境刺激等多重因素，這些因素共同導(dǎo)致CD8?T細(xì)胞異常活化，最終引發(fā)表皮黑素細(xì)胞破壞。因此，針對T細(xì)胞的靶向治療成為研究焦點。近期FDA批準(zhǔn)的多種JAK抑制劑通過抑制CD8?T細(xì)胞募集，在改善白斑病患者復(fù)色方面顯示出療效。盡管II/III期臨床試驗證實這些療法可顯著改善皮膚色素沉著，但患者應(yīng)答存在個體差異，且鮮有實現(xiàn)持久的色素再生。

氯膦酸鹽二鈉脂質(zhì)體清除單核巨噬細(xì)胞，在白斑病模型中單核巨噬細(xì)胞功能研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

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.