脱发有救了!Nature子刊揭示:这种免疫细胞竟然是头发再生的关键

2022-07-03 Swagpp MedSci原创

自然·免疫学:调节性T细胞(regulatory T cell,Treg细胞)能够感受脱发部位糖皮质激素水平变化,释放TGF-β3,激活毛囊干细胞增殖,毛囊由休止期进入生长期,头皮焕发生机。

头发脱落,
是风的追求,
还是头皮的不挽留,
花儿谢了明年还是一样的开,
我的秀发一去,还回得来吗?
要想生发,就需要毛囊内的“种子”——毛囊干细胞能够源源不断生成新发。但是,光有毛囊干细胞还不够,因为在大部分时间里,毛囊干细胞都是处于一个休眠的状态,如果不能唤醒沉睡的毛囊干细胞,一样要面临“后继无发”的悲剧。
要能有一位管家能够及时唤醒毛囊干细胞,那是再好不过了。
诶,还别说,真有这么一种细胞在毛囊干细胞周围担任管家一职,近期来自美国Salk研究所的科学家就发现调节性T细胞(regulatory T cell,Treg细胞)能够感受脱发部位糖皮质激素水平变化,释放TGF-β3,激活毛囊干细胞增殖,毛囊由休止期进入生长期,头皮焕发生机。该研究发表于《自然·免疫学》。
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Treg细胞早期又被称为抑制性T细胞,是一类负调节机体免疫反应的T淋巴细胞,对维持自身耐受和限制免疫反应过度起着重要作用,但也参与肿瘤细胞的免疫逃逸和慢性感染。除此之外,Treg细胞同时还肩负着另一重功能,那就是维持组织稳定,促进组织修复和再生。
而糖皮质激素作为临床上使用最为广泛的抗炎和免疫抑制剂,长期使用的副作用除了有满月脸,水牛背之外,还有一点就是多毛症!
糖皮质激素与毛发的联系还不止于此,抓一只小鼠给它脱毛,脱毛区局部皮肤内糖皮质激素水平会短暂上升,同时毛囊干细胞周围的Treg细胞上的糖皮质激素受体的表达非常高,而这一切恰好就赶在了毛囊干细胞活化的时间点,要说它们仨没有联系,那反正研究人员是不太信的。
图片
注:脱毛后皮肤局部糖皮质激素水平在48小时内迅速升高,血液中的糖皮质激素水平则没有变化
为了研究糖皮质激素和Treg细胞在生发过程中起到怎样的作用,他们选择将小鼠Treg细胞上的糖皮质激素受体敲除(GR cKO),切断Treg细胞和糖皮质激素之间的直接联系,然后给小鼠背部脱毛。
在脱毛后第15天,正常小鼠背部毛发就已经“春风吹又生”,而GR cKO小鼠毛发只长了不到20%。
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注:脱毛后15天,两组小鼠毛发再生情况
组织学显示正常小鼠新生毛发明显要长于GR cKO小鼠,且已经突破真皮脂肪层野蛮生长了,而GR cKO小鼠的毛囊细胞还未破“土”而出。
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进一步分析正常小鼠和GR cKO小鼠毛囊干细胞的状态,脱毛后正常小鼠毛囊干细胞迅速从休眠状态激活,细胞增殖、分化基因表达上升,Ki67、EdU染色增加标志着毛囊干细胞开始分裂,毛囊由休止期进入到生发期。反观脱毛后的GR cKO小鼠,增殖的毛囊干细胞寥寥无几。
以上现象说明:敲除了Treg细胞上的糖皮质激素受体,将导致脱毛后毛囊干细胞不能正常增殖,毛发再生困难。
图片
为什么敲除Treg细胞上的糖皮质激素受体会对毛囊干细胞产生如此大的影响?
研究人员先是分析敲除糖皮质激素受体后,Treg细胞免疫调节功能是否受损。体内、体外实验结果均证明糖皮质激素受体敲除一点不影响Treg细胞发挥免疫抑制作用,“敲除Treg细胞糖皮质激素受体使得Treg细胞免疫功能障碍,毛囊干细胞周围环境免疫失衡,进一步引起毛囊干细胞一蹶不振”的猜想就此告吹。
接下来研究人员又猜测Treg细胞上的糖皮质激素受体可能对Treg细胞释放某种因子,激活毛囊干细胞至关重要。分析脱毛后正常小鼠、GR cKO小鼠Treg细胞、毛囊干细胞之间可能存在的信号通路,研究人员发现,脱毛后正常小鼠的Treg细胞TGF-β3表达量增加,促进毛囊干细胞内BMP信号通路由脱毛前抑制生发的pSmad1/5向激活生发的pSmad2/3转变,而在GR cKO小鼠脱毛前后Treg细胞和毛囊干细胞则没有发生类似的改变。
进一步的验证实验中,研究人员向正常小鼠脱毛区注射TGF-β3中和抗体,正常小鼠脱毛区的注射部位也变得像GR cKO小鼠一样寸草不生;而如果向GR cKO小鼠脱毛区注射TGF-β3,就能看到GR cKO小鼠脱毛区注射部位终于沙漠变绿洲,毛囊干细胞总算是醒了。
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总结一下,这篇研究讲的其实就是头发脱落后,脱发区局部糖皮质激素会增加,糖皮质激素和Treg细胞上的糖皮质激素受体结合,促进Treg细胞分泌TGF-β3,激活毛囊干细胞进入增殖状态,毛发再生。唤醒沉睡的毛囊干细胞,管家Treg细胞功不可没。
实际上,在临床中糖皮质激素早已被用来治疗斑秃,只不过大家都以为糖皮质激素发挥主要作用就是抑制免疫细胞功能,避免免疫细胞攻击毛囊,降低头皮炎症反应。这是科学家第一次发现糖皮质激素治疗脱发的过程中,还能与Treg细胞产生联系。
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参考资料:

Liu Z, Hu X, Liang Y, et al. Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle stem-cell niche [published online ahead of print, 2022 Jun 23]. Nat Immunol. 2022;10.1038/s41590-022-01244-9. doi:10.1038/s41590-022-01244-9

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    2023-02-13 liye789132251
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    2022-07-05 1801f26e0em

    用什么药治疗脱发呢?

    0

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    2022-07-04 qindq
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    2022-07-03 huaguang

    激活毛囊干细胞增值就能使毛囊进去生长期

    0

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    2022-07-03 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2022-07-03 ms6000000960504356

    不错的文章

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