Bone marrow (BM)-mediated trained innate immunity (TII) is a state of heightened immune responsiveness of hematopoietic stem and progenitor cells (HSPC) and their myeloid progeny. We show here that maladaptive BM-mediated TII underlies inflammatory comorbidities, as exemplified by the periodontitis-arthritis axis. Experimental-periodontitis-related systemic inflammation in mice induced epigenetic rewiring of HSPC and led to sustained enhancement of production of myeloid cells with increased inflammatory preparedness. The periodontitis-induced trained phenotype was transmissible by BM transplantation to naive recipients, which exhibited increased inflammatory responsiveness and disease severity when subjected to inflammatory arthritis. IL-1 signaling in HSPC was essential for their maladaptive training by periodontitis. Therefore, maladaptive innate immune training of myelopoiesis underlies inflammatory comorbidities and may be pharmacologically targeted to treat them via a holistic approach.

骨髓（BM）介导的训练有素的先天免疫（TII）是造血干细胞和祖细胞（HSPC）及其骨髓后代的免疫反应性增强的状态。我们在此表明​​，适应不良的 BM 介导的 TII 是炎症合并症的基础，如牙周炎-关节炎轴所示。小鼠实验性牙周炎相关全身炎症诱导 HSPC 表观遗传重连，导致骨髓细胞生成持续增强，炎症准备能力增强。牙周炎诱导的训练表型可通过骨髓移植传播给初始接受者，当遭受炎性关节炎时，其表现出增加的炎症反应性和疾病严重程度。 HSPC 中的 IL-1 信号传导对于牙周炎引起的适应不良训练至关重要。因此，骨髓生成的适应不良的先天免疫训练是炎症合并症的基础，并且可以通过整体方法进行药理学靶向治疗。