Mou Rong, Ma Junkai, Ju Xuan, Wu Yixin, Chen Qiuli, Li Jinglin, Shang Tongyao, Chen Siying, Yang Yue, Li Yue, Lv Kaosheng, Chen Xuequn, Zhang Qi, Liang Tingbo, Feng Ye, Lu Xinjiang
Department of Physiology and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China.
Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou 310013, Zhejiang, China.
Cell Stem Cell. 2024 Dec 5;31(12):1794-1812.e10. doi: 10.1016/j.stem.2024.09.018. Epub 2024 Oct 22.
Psychological stress is often linked to depression and can also impact the immune system, illustrating the interconnectedness of mental health and immune function. Hematopoietic stem cells (HSCs) can directly sense neuroendocrine signals in bone marrow and play a fundamental role in the maintenance of immune homeostasis. However, it is unclear how psychological stress impacts HSCs in depression. Here, we report that neuroendocrine factor arginine vasopressin (AVP) promotes myeloid-biased HSC differentiation by activating neutrophils. AVP administration increases neutrophil and Ly6C monocyte production by triggering HSCs that rely on intrinsic S100A9 in mice. When stimulated with AVP, neutrophils return to the bone marrow and release interleukin 36G (IL-36G), which interacts with interleukin 1 receptor-like 2 (IL-1RL2) on HSCs to produce neutrophils with high Elane expression that infiltrate the brain and induce neuroinflammation. Together, these findings define HSCs as a relay between psychological stress and myelopoiesis and identify the IL-36G-IL-1RL2 axis as a potential target for depression therapy.
心理压力常常与抑郁症相关联，并且还会影响免疫系统，这说明了心理健康与免疫功能之间的相互联系。造血干细胞（HSCs）能够直接感知骨髓中的神经内分泌信号，并在维持免疫稳态中发挥重要作用。然而，目前尚不清楚心理压力如何在抑郁症中影响造血干细胞。在此，我们报告神经内分泌因子精氨酸加压素（AVP）通过激活中性粒细胞促进偏向髓系的造血干细胞分化。在小鼠中，给予AVP通过触发依赖内在S100A9的造血干细胞来增加中性粒细胞和Ly6C单核细胞的产生。当受到AVP刺激时，中性粒细胞返回骨髓并释放白细胞介素36G（IL-36G），其与造血干细胞上的白细胞介素1受体样2（IL-1RL2）相互作用，产生具有高Elane表达的中性粒细胞，这些中性粒细胞浸润大脑并诱导神经炎症。总之，这些发现将造血干细胞定义为心理压力与髓系造血之间的一个中继，并确定IL-36G-IL-1RL2轴作为抑郁症治疗的一个潜在靶点。
