Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities

Xiaofei Li, Hui Wang, Xiang Yu, Gundappa Saha, Lydia Kalafati, Charalampos Ioannidis, Ioannis Mitroulis, Mihai G. Netea, Triantafyllos Chavakis, George Hajishengallis

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
JournalCell
Early online date27 Apr 2022
DOIs
Publication statusPublished - 12 May 2022

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