美国哈佛大学Ya-Chieh Hsu研究组提出了应激诱导的交感神经过度激活驱动毛囊坏死触发自身免疫。该研究于2025年11月26日发表于国际一流学术期刊《细胞》杂志上。
研究人员发现急性压力会引发快速脱发并引发自身免疫。在压力下，过度激活的交感神经释放过量的去甲肾上腺素，导致快速分裂的毛囊转运扩增细胞（HF-TACs）发生导管坏死，同时保留大多数毛囊干细胞（HFSCs）。这种不同的敏感性源于细胞死亡途径、代谢策略和钙稳态的差异，这使得HF-TACs更容易受到去甲肾上腺素诱导的钙激增的影响。HF-TAC坏死释放细胞碎片，触发巨噬细胞介导的清除和树突状细胞激活，最终导致自身反应性T细胞的激活和扩增，从而在炎症损伤下攻击毛囊。他们的发现揭示了压力如何通过交感神经诱导的坏死，在高度增殖的HF-TACs中引起立即组织损伤的机制，这反过来又刺激了自身反应性T细胞的激活，这些T细胞能够在未来对同一组织发动攻击。
研究人员表示，压力对健康有着深远的影响，但人们对它是如何损害组织的却知之甚少。
附：英文原文
Title: Stress-induced sympathetic hyperactivation drives hair follicle necrosis to trigger autoimmunity
Author: Emily Scott-Solomon, Shlomi Brielle, Alexander O. Mann, Mark J. Khoury, Jingyu Peng, Liana Tellez, Mackenzie Harrigan, Myrto Ziogas, H. Amalia Pasolli, Monica Cassandras, Adam J. Getzler, Rebecca Freeman, Bing Zhang, Yulia Shwartz, Judith Agudo, Ruth A. Franklin, Ya-Chieh Hsu
Issue&Volume: 2025-11-26
Abstract: Stress has profound effects on health, yet how it damages tissues remains poorly understood. Here, we show that acute stress triggers rapid hair loss and initiates autoimmunity. Under stress, hyperactivated sympathetic nerves release excessive norepinephrine, causing necrosis in rapidly dividing hair follicle transit-amplifying cells (HF-TACs) while sparing most hair follicle stem cells (HFSCs). This differential sensitivity stems from differences in cell death pathways, metabolic strategies, and calcium homeostasis, which render HF-TACs more susceptible to norepinephrine-induced calcium surges. HF-TAC necrosis releases cellular debris that triggers macrophage-mediated clearance and dendritic cell activation, ultimately leading to the activation and amplification of autoreactive T cells that can attack the hair follicle under inflammatory insults. Our findings reveal mechanistically how stress causes immediate tissue damage in highly proliferative HF-TACs via sympathetic nerve-induced necrosis, which in turn fuels the activation of autoreactive T cells capable of mounting future attacks against the same tissue.
DOI: 10.1016/j.cell.2025.10.042
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01247-4