Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities

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-...

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Published in:Cell Vol. 185; no. 10; p. 1709
Main Authors: Li, Xiaofei, Wang, Hui, Yu, Xiang, Saha, Gundappa, Kalafati, Lydia, Ioannidis, Charalampos, Mitroulis, Ioannis, Netea, Mihai G, Chavakis, Triantafyllos, Hajishengallis, George
Format: Journal Article
Language:English
Published: United States 12.05.2022
Subjects:
Animals
Arthritis
Hematopoietic Stem Cells
Immunity, Innate
Mice
Myelopoiesis
Periodontitis
arthritis
comorbidities
inflammation
myelopoiesis
periodontitis
hematopoietic stem and progenitor cells
epigenetic rewiring
trained immunity
bone marrow transplantation
ISSN:1097-4172, 1097-4172
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Summary: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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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2022.03.043