Nature子刊:郑页团队发现头发生长与免疫系统间的惊人联系

2022-06-24 生物世界 生物世界

该研究揭示了在皮肤毛囊损伤的情况下诱导产生的糖皮质激素(glucocorticoid)可以促进调节性T细胞(Treg)分泌生长因子 TGF-β3,进而促进毛囊干细胞增殖以及毛发再生。

2022年6月23日,美国索尔克生物研究所郑页课题组在 Nature 子刊 Nature Immunology 在线发表了题为:Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle stem-cell niche(糖皮质激素和调节性T细胞协同维持毛囊干细胞微环境)的研究论文。

该研究揭示了在皮肤毛囊损伤的情况下诱导产生的糖皮质激素(glucocorticoid)可以促进调节性T细胞(Treg)分泌生长因子 TGF-β3,进而促进毛囊干细胞增殖以及毛发再生。

该研究不仅拓宽了人们对组织驻留调节性T细胞如何发挥非免疫抑制功能的认知,还对理解斑秃(一种免疫系统攻击自身毛囊而导致的脱发)的发病机制以及糖皮质激素治疗斑秃的分子机理有重要的指导意义。

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调节性T细胞(Treg)长期以来被认为是一群具有抑制机体过度免疫反应功能的淋巴细胞,对维持机体免疫耐受至关重要。近年来,研究显示调节性T细胞除了发挥免疫抑制功能之外,还可以在非淋巴组织中调节机体的代谢和组织修复与再生。然而调节性T细胞如何促进损伤组织的修复和再生并不清楚。尤其是无法确定调节性T细胞是否不依赖其免疫抑制功能,而直接通过调节组织干细胞的增殖与分化来促进组织的修复与再生。

在这项研究中,论文第一作者刘志博士等研究人员利用皮肤毛囊损伤与修复这一模型, 致力于寻找在组织损伤的情况下,什么信号通路可以诱导调节性T细胞的促再生(pro- regenerative)功能,以及调节性T细胞通过分泌什么生长因子来促进毛囊干细胞的增殖与分化。

在该研究中,研究人员首先观察到糖皮质激素受体(glucocorticoid receptor)在皮肤中的调节性T细胞高表达,以及对皮肤毛囊进行脱毛损伤后诱导分泌的糖皮质激素水平增高。这些结果提示糖皮质激素信号可能在调节性T细胞促进毛发再生过程中发挥重要的作用。

接下来,研究人员发现糖皮质激素受体的条件性敲除小鼠的毛发,在脱毛损伤下或者自然毛发生长周期中,无法像野生型小鼠一样正常再生或生长,毛囊干细胞一直处于休眠状态,无法被激活,增殖与分化

令人意外的是,虽然糖皮质激素在临床上被用于抑制炎症性疾病,以及调节性T细胞的经典功能就是抑制过度免疫反应,但是该项研究发现内源性的糖皮质激素并影响调节性T细胞的免疫调节功能,进而提示糖皮质激素可以直接诱导调节性T细胞的促再生功能。

下一步,研究人员发现,调节性T细胞受到糖皮质激素信号激活后分泌的细胞生长因子 TGF-β3 可能直接介导调节性T细胞和毛囊干细胞之间的交流。

最后,研究人员通过体外调节性T细胞对毛囊干细胞的共培养实验,体内给予外源性的 TGF-β3 或者阻断 TGF-β3 信号通路,以及 TGF-β3 条件性敲除小鼠确定了调节性T细胞分泌的 TGF-β3 介导了调节性T细胞对毛囊干细胞的调控以及促进毛发再生

图片

糖皮质激素诱导调节性T细胞与组织干细胞相互作用促进毛发生长

综上,该研究揭示了诱导调节性T细胞和毛囊干细胞相互作用的上游激素信号——糖皮质激素,以及介导他们交流的下游生长因——TGF-β3,明确了诱导调节性T细胞的促组织再生功能的信号通路可以独立于调节其免疫抑制功能的TCR信号或者细胞因子信号通路,进而证实了调节性T细胞可以不依赖其维持组织微环境免疫稳态的功能,直接调节组织干细胞的增殖分化以及组织的修复和再生。

该研究对如何利用调节性T细胞治疗斑秃,创伤修复,以及如何干预机体衰老和器官修复都有重要的借鉴作用。

索尔克生物研究所郑页研究员为论文通讯作者,博士后刘志为第一作者。胡娴亭博士等其他实验室成员也参与了该项工作,该研究还得到了复旦大学眼耳鼻喉医院的李华斌教授的大力支持。

论文链接:

https://www.nature.com/articles/s41590-022-01244-9

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    2023-04-10 liye789132251
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    2022-06-26 qindq
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    2022-06-26 huaguang

    毛囊干细胞无法被激活

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    2022-06-25 weigq

    学习

    0

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    2022-06-24 ms5000000644045955

    不错,学习了。

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    2022-06-24 屋顶瞄爱赏月

    签到学习

    0

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