Liao Weinian, Zai Xiaodong, Zhang Jun, Xu Junjie
Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, 100071, China.
Cell Commun Signal. 2025 Apr 14;23(1):182. doi: 10.1186/s12964-025-02192-1.
Trained immunity serves as a de facto memory for innate immune responses, resulting in long-term functional reprogramming of innate immune cells. It enhances resistance to pathogens and augments immunosurveillance under physiological conditions. Given that innate immune cells typically have a short lifespan and do not divide, persistent innate immune memory may be mediated by epigenetic and metabolic changes in long-lived hematopoietic stem cells (HSCs) in the bone marrow. HSCs fine-tune their state and fate in various training conditions, thereby generating functionally adapted progeny cells that orchestrate innate immune plasticity. Notably, both beneficial and maladaptive trained immunity processes can comprehensively influence HSC state and fate, leading to divergent hematopoiesis and immune outcomes. However, the underlying mechanisms are still not fully understood. In this review, we summarize recent advances regarding HSC state and fate in the context of trained immunity. By elucidating the stem cell-intrinsic and extrinsic regulatory network, we aim to refine current models of innate immune memory and provide actionable insights for developing targeted therapies against infectious diseases and chronic inflammation. Furthermore, we propose a conceptual framework for engineering precision-trained immunity through HSC-targeted interventions.
训练有素的免疫作为先天免疫反应的一种实际记忆，导致先天免疫细胞的长期功能重编程。它增强了对病原体的抵抗力，并在生理条件下增强了免疫监视。鉴于先天免疫细胞通常寿命较短且不分裂，持久的先天免疫记忆可能由骨髓中长寿造血干细胞（HSC）的表观遗传和代谢变化介导。造血干细胞在各种训练条件下微调其状态和命运，从而产生协调先天免疫可塑性的功能适应性子代细胞。值得注意的是，有益和适应不良的训练有素的免疫过程都可以全面影响造血干细胞的状态和命运，导致不同的造血和免疫结果。然而，其潜在机制仍未完全了解。在这篇综述中，我们总结了训练有素的免疫背景下造血干细胞状态和命运的最新进展。通过阐明干细胞内在和外在调节网络，我们旨在完善当前的先天免疫记忆模型，并为开发针对传染病和慢性炎症的靶向疗法提供可行的见解。此外，我们提出了一个通过造血干细胞靶向干预来设计精确训练免疫的概念框架。
