Yao Hang, Liu Yang, Wang Yueping, Xue You, Jiang Siyuan, Sun Xin, Ji Minjun, Xu Zhipeng, Ding Jianhua, Hu Gang, Lu Ming
Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
The Second People's Hospital of Changzhou, Changzhou Medical Center, Nanjing Medical University, Nanjing, China.
Cell Death Differ. 2025 May;32(5):926-943. doi: 10.1038/s41418-024-01421-3. Epub 2024 Nov 27.
The dura sinus-resident immune cells can influence the process of central neural system (CNS) diseases by communicating with central nerve cells. In clinical, Tregs are also frequently impaired in depression. However, the significance of this relationship remains unknown. In the present study, we found a significant increase in dural Treg populations in mouse models of depression, whereas depleting them by neutralizing antibodies injection could exacerbate depressive phenotypes. Through RNA sequencing, we identified that the antidepressant effects of dural Tregs are at least in part through the production of amphiregulin, increasing the expression of its receptor EGFR in medial prefrontal cortex (mPFC) pyramidal neurons. Furthermore, dural Tregs expressed high levels of ST2, and their expansion in depressed mice depended on astrocyte-derived IL33 secretion. Our study shows that dural Treg signaling can be enhanced by treatment with fluoxetine, highlighting that dural Tregs can be utilized as a potential target cell in major depressive disorder (MDD).
硬脑膜窦驻留免疫细胞可通过与中枢神经细胞通讯来影响中枢神经系统（CNS）疾病的进程。在临床上，抑郁症患者的调节性T细胞（Tregs）也常常受损。然而，这种关系的意义仍不清楚。在本研究中，我们发现抑郁症小鼠模型中硬脑膜Treg群体显著增加，而通过注射中和抗体消耗它们会加剧抑郁表型。通过RNA测序，我们确定硬脑膜Tregs的抗抑郁作用至少部分是通过产生双调蛋白，增加其受体表皮生长因子受体（EGFR）在内侧前额叶皮质（mPFC）锥体神经元中的表达。此外，硬脑膜Tregs表达高水平的ST2，它们在抑郁小鼠中的扩增依赖于星形胶质细胞衍生的白细胞介素33（IL33）分泌。我们的研究表明，氟西汀治疗可增强硬脑膜Treg信号传导，突出了硬脑膜Tregs可作为重度抑郁症（MDD）的潜在靶细胞。
