| First Author | Li X | Year | 2022 |
| Journal | Cell | Volume | 185 |
| Issue | 10 | Pages | 1709-1727.e18 |
| PubMed ID | 35483374 | Mgi Jnum | J:325686 |
| Mgi Id | MGI:7281644 | Doi | 10.1016/j.cell.2022.03.043 |
| Citation | Li X, et al. (2022) Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities. Cell 185(10):1709-1727.e18 |
| abstractText | 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. |
