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^hi 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.

中文翻译：

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加压素驱动造血干细胞的异常髓样分化，导致小鼠抑郁


心理压力通常与抑郁症有关，也会影响免疫系统，这说明了心理健康和免疫功能之间的相互关联。造血干细胞 （HSCs） 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重要作用。然而，目前尚不清楚心理压力如何影响抑郁症中的 HSC。在这里，我们报道了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骨髓偏向性 HSC 分化。AVP 给药通过触发依赖于小鼠内在 S100A9 的 HSC 来增加中性粒细胞和 Ly6C^hi 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），它与 HSC 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，浸润大脑并诱导神经炎症。总之，这些发现将 HSC 定义为心理压力和骨髓生成之间的中继，并将 IL-36G-IL-1RL2 轴确定为抑郁症治疗的潜在靶点。