骨髓生成
先天免疫系统
免疫学
髓样
生物
炎症
牙周炎
造血
免疫系统
关节炎
骨髓
炎性关节炎
医学
干细胞
内科学
细胞生物学
作者
Xiaofei Li,Hui Wang,Xiang Yu,Gundappa Saha,Lydia Kalafati,Charalampos Ioannidis,Ioannis Mitroulis,Mihai G. Netea,Triantafyllos Chavakis,George Hajishengallis
出处
期刊:Cell
[Elsevier]
日期:2022-05-01
卷期号:185 (10): 1709-1727.e18
被引量:97
标识
DOI:10.1016/j.cell.2022.03.043
摘要
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.
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