浙江大学陆新江等研究人员合作发现，抗利尿激素驱动造血干细胞的异常髓系分化从而导致小鼠抑郁症状。2024年10月22日，《细胞—干细胞》杂志在线发表了这项成果。

研究人员报告神经内分泌因子精氨酸抗利尿激素（AVP）通过激活中性粒细胞促进造血干细胞（HSC）髓系偏向分化。AVP的给药通过触发依赖于内源性S100A9的HSC，增加中性粒细胞和Ly6C^hi单核细胞的产生。

当中性粒细胞受到AVP刺激时，它们返回骨髓并释放白细胞介素36G（IL-36G），该因子与HSC上的白细胞介素1受体样蛋白2（IL-1RL2）相互作用，促使产生高Elane表达的中性粒细胞，这些细胞渗透至大脑并诱导神经炎症。

综合来看，这些发现将HSC定义为心理压力与髓系生成之间的中介，并识别IL-36G-IL-1RL2轴作为抑郁治疗的潜在靶点。

研究人员表示，心理压力通常与抑郁相关，并且会影响免疫系统，反映了心理健康与免疫功能之间的相互联系。HSC可以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基础作用。然而，心理压力如何影响抑郁症中的HSC尚不明确。

附：英文原文

Title: Vasopressin drives aberrant myeloid differentiation of hematopoietic stem cells, contributing to depression in mice

Author: Rong Mou, Junkai Ma, Xuan Ju, Yixin Wu, Qiuli Chen, Jinglin Li, Tongyao Shang, Siying Chen, Yue Yang, Yue Li, Kaosheng Lv, Xuequn Chen, Qi Zhang, Tingbo Liang, Ye Feng, Xinjiang Lu

Issue&Volume: 2024-10-22

Abstract: 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 Ly6Chi 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.

DOI: 10.1016/j.stem.2024.09.018

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00358-8