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Haacke, N.* ; Wang, H.* ; Yan, S.* ; Barovic, M.* ; Li, X.* ; Nagai, K.* ; Botezatu, A.* ; Hatzioannou, A.* ; Gercken, B.* ; Trimaglio, G.* ; Shah, A.U.* ; Wang, J.* ; Ye, L.* ; Jaykar, M.T.* ; Rauner, M.* ; Wielockx, B.* ; Chung, K.J.* ; Netea, M.G.* ; Kalafati, L.* ; Hajishengallis, G.* ; Chavakis, T.

Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice.

Dev. Cell 60, 1854-1870 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
We previously demonstrated that long-term trained immunity (TRIM) involves adaptations that imprint innate immune memory in long-lived myelopoiesis precursors and their progeny, monocytes/macrophages and neutrophils, which thereby acquire enhanced responsiveness to future challenges. Here, we show that a distinct component of myeloid biology, osteoclastogenesis, can also undergo innate immune training. Indeed, β-glucan-induced TRIM was associated with an increased osteoclastogenesis bias in the bone marrow and an expansion of monocytes/osteoclast progenitors in the periphery, resulting in aggravated severity of experimental periodontitis and arthritis. In the setting of trained inflammatory osteoclastogenesis, we observed transcriptomic rewiring in synovial myeloid cells of arthritic mice, featuring prominent upregulation of the transcription factor melanogenesis-associated transcription factor (MITF). Adoptive transfer of splenic monocytes from β-glucan-trained mice to naive recipients exacerbated arthritis in the latter in a strictly MITF-dependent manner. Our findings establish trained osteoclastogenesis as a maladaptive component of TRIM and potentially provide therapeutic targets in inflammatory bone loss disorders.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Inflammatory Bone Loss ; Innate Immune Memory ; Monocytes ; Osteoclastogenesis ; Trained Immunity; Autoimmune Arthritis; Hematopoietic Stem; Progenitor Cells; Dendritic Cells; Induction; Differentiation; Macrophages; Activation; Glucan; Identification
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Journal Developmental Cell
Quellenangaben Volume: 60, Issue: 13, Pages: 1854-1870 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
Grants Saxon State Ministry of Science, Culture and Tourism (SMWK)
European Research Council (LOSYSINCHRON)
NIH
Deutsche Forschungsgemeinschaft
Stiftung fur Pathobiochemie und Molekulare Diagnostik