Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities.

Abstract

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.

• Authors: Xiaofei Li, Hui Wang, Xiang Yu, Gundappa Saha, Lydia Kalafati, Charalampos Ioannidis, Ioannis Mitroulis, Mihai G Netea, Triantafyllos Chavakis, George Hajishengallis
• Journal: Cell (Cell) Vol. 185 Issue 10 Pg. 1709-1727.e18 (05 12 2022) ISSN: 1097-4172 [Electronic] United States
• PMID: 35483374 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Topics

• Animals
• Arthritis
• Hematopoietic Stem Cells
• Immunity, Innate
• Mice
• Myelopoiesis
• Periodontitis