Imperial College London
Alternate

DrJacquesBehmoaras

Faculty of Medicine, Department of Immunology and Inflammation

Reader in Immunogenetics
 
 
 
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Contact

 

+44 (0)20 3313 2339jacques.behmoaras Website

 
 
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Location

 

9N13Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Behmoaras:2023:10.15252/embr.202256310,
author = {Behmoaras, J},
doi = {10.15252/embr.202256310},
journal = {EMBO Reports},
pages = {1--19},
title = {Multinucleation resets human macrophages for specialized functions at the expense of their identity},
url = {http://dx.doi.org/10.15252/embr.202256310},
volume = {24},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Macrophages undergo plasma membrane fusion and cell multinucleation to form multinucleated giant cells (MGCs) such as osteoclasts in bone, Langhans giant cells (LGCs) as part of granulomas or foreign-body giant cells (FBGCs) in reaction to exogenous material. How multinucleation per se contributes to functional specialization of mature mononuclear macrophages remains poorly understood in humans. Here, we integrate comparative transcriptomics with functional assays in purified mature mononuclear and multinucleated human osteoclasts, LGCs and FBGCs. Strikingly, in all three types of MGCs, multinucleation causes a pronounced downregulation of macrophage identity. We show enhanced lysosome-mediated intracellular iron homeostasis promoting MGC formation. The transition from mononuclear to multinuclear state is accompanied by cell specialization specific to each polykaryon. Enhanced phagocytic and mitochondrial function associate with FBGCs and osteoclasts, respectively. Moreover, human LGCs preferentially express B7-H3 (CD276) and can form granuloma-like clusters in vitro, suggesting that their multinucleation potentiates T cell activation. These findings demonstrate how cell–cell fusion and multinucleation reset human macrophage identity as part of an advanced maturation step that confers MGC-specific functionality.
AU  - Behmoaras,J
DO  - 10.15252/embr.202256310
EP  - 19
PY  - 2023///
SN  - 1469-221X
SP  - 1
TI  - Multinucleation resets human macrophages for specialized functions at the expense of their identity
T2  - EMBO Reports
UR  - http://dx.doi.org/10.15252/embr.202256310
UR  - https://www.embopress.org/doi/full/10.15252/embr.202256310
UR  - http://hdl.handle.net/10044/1/102210
VL  - 24
ER  -
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