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

梅斯头条

企业/

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》。

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。

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%。

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。

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。

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。

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。

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

#Nat#

81 0
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2022-07-05 1801f26e0em

用什么药治疗脱发呢？

82 0
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2022-07-04 qindq

#头发#

93 0
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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

78 0
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2022-07-03 1209e435m98(暂无昵称)

学习了，谢谢分享

76 0
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2022-07-03 ms6000000960504356

#期刊论坛##学习#

123 0
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2022-07-03 ms6000000960504356

不错的文章

107 0
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2022-07-03 病毒猎手

#脱发#

119 0

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