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

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2024-10-22 DOI:10.1016/j.stem.2024.09.018
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
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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.

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血管加压素促使造血干细胞骨髓分化异常,导致小鼠抑郁
心理压力通常与抑郁有关,也会影响免疫系统,这说明心理健康与免疫功能是相互关联的。造血干细胞(HSCs)能直接感知骨髓中的神经内分泌信号,并在维持免疫平衡方面发挥着重要作用。然而,目前还不清楚心理压力如何影响抑郁症患者的造血干细胞。在这里,我们报告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髓系造血干细胞分化。给小鼠注射 AVP 可通过触发依赖于内在 S100A9 的造血干细胞来增加中性粒细胞和 Ly6Chi 单核细胞的生成。当受到 AVP 刺激时,中性粒细胞会返回骨髓并释放白细胞介素 36G(IL-36G),它与造血干细胞上的白细胞介素 1 受体样 2(IL-1RL2)相互作用,产生高 Elane 表达的中性粒细胞,这些中性粒细胞会浸润大脑并诱发神经炎症。这些发现共同确定了造血干细胞是心理压力和骨髓造血之间的中继站,并确定了IL-36G-IL-1RL2轴是抑郁症治疗的潜在靶点。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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