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Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair

Federico Francesco De Ponti (UGent) , Anna Bujko (UGent) , Zhuangzhuang Liu (UGent) , Paul Collins (UGent) , Sara Schuermans, Christian Maueröder (UGent) , Seraja Amstelveen (UGent) , Tinne Thoné (UGent) , Liesbet Martens (UGent) , John McKendrick (UGent) , et al.
(2025) IMMUNITY. 58(2). p.362-380
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Abstract
Our understanding of the functional heterogeneity of resident versus recruited macrophages in the diseased liver is limited. A population of recruited lipid-associated macrophages (LAMs) has been reported to populate the diseased liver alongside resident Kupffer cells (KCs). However, the precise roles of these distinct macrophage subsets remain elusive. Here, using proteogenomics, we have identified LAMs in multiple models of liver injury. Moreover, we found that this phenotype is not specific to recruited macrophages, as a subset of resident KCs can also adopt a LAM-like phenotype in the mouse and human liver. By combining genetic mouse models targeting the distinct populations, we determined that both recruited LAMs and resident LAM-like KCs play crucial roles in tissue repair. Specifically, triggering receptor expressed on myeloid cells 2 (TREM2) expression on either resident or recruited macrophages is required for the efficient clearance of dying cells, enhancing repair and preventing exacerbated fibrosis.
Keywords
KUPFFER CELLS, LIVER, LANDSCAPE, MICROGLIA, TREM2, DEFICIENT, DIVERSITY, BIOLOGY, DRIVES, MODEL

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MLA
De Ponti, Federico Francesco, et al. “Spatially Restricted and Ontogenically Distinct Hepatic Macrophages Are Required for Tissue Repair.” IMMUNITY, vol. 58, no. 2, 2025, pp. 362–80, doi:10.1016/j.immuni.2025.01.002.
APA
De Ponti, F. F., Bujko, A., Liu, Z., Collins, P., Schuermans, S., Maueröder, C., … Scott, C. (2025). Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair. IMMUNITY, 58(2), 362–380. https://doi.org/10.1016/j.immuni.2025.01.002
Chicago author-date
De Ponti, Federico Francesco, Anna Bujko, Zhuangzhuang Liu, Paul Collins, Sara Schuermans, Christian Maueröder, Seraja Amstelveen, et al. 2025. “Spatially Restricted and Ontogenically Distinct Hepatic Macrophages Are Required for Tissue Repair.” IMMUNITY 58 (2): 362–80. https://doi.org/10.1016/j.immuni.2025.01.002.
Chicago author-date (all authors)
De Ponti, Federico Francesco, Anna Bujko, Zhuangzhuang Liu, Paul Collins, Sara Schuermans, Christian Maueröder, Seraja Amstelveen, Tinne Thoné, Liesbet Martens, John McKendrick, Pieter Louwe, Ana Sánchez Cruz, Wouter Saelens, Kylie P. Matchett, Kathryn Waller, Christian Zwicker, Aimee-Rose Bugler-Lamb, Bavo Vanneste, Fleur Parmentier, Mushida Binte Abdul Latib, Anneleen Remmerie, Lénárd Kertész, Anna Kremer, Jérémy Verbeke, David Højland Ipsen, Dominik Reinhard Pfister, Zhaoyuan Liu, Martin Guilliams, Neil C. Henderson, Kodi Ravichandran, Pedro E. Marques, and Charlotte Scott. 2025. “Spatially Restricted and Ontogenically Distinct Hepatic Macrophages Are Required for Tissue Repair.” IMMUNITY 58 (2): 362–380. doi:10.1016/j.immuni.2025.01.002.
Vancouver
1.
De Ponti FF, Bujko A, Liu Z, Collins P, Schuermans S, Maueröder C, et al. Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair. IMMUNITY. 2025;58(2):362–80.
IEEE
[1]
F. F. De Ponti et al., “Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair,” IMMUNITY, vol. 58, no. 2, pp. 362–380, 2025.
@article{01JN3CAG13F72T83QZ0ZR8M0N1,
  abstract     = {{Our understanding of the functional heterogeneity of resident versus recruited macrophages in the diseased liver is limited. A population of recruited lipid-associated macrophages (LAMs) has been reported to populate the diseased liver alongside resident Kupffer cells (KCs). However, the precise roles of these distinct macrophage subsets remain elusive. Here, using proteogenomics, we have identified LAMs in multiple models of liver injury. Moreover, we found that this phenotype is not specific to recruited macrophages, as a subset of resident KCs can also adopt a LAM-like phenotype in the mouse and human liver. By combining genetic mouse models targeting the distinct populations, we determined that both recruited LAMs and resident LAM-like KCs play crucial roles in tissue repair. Specifically, triggering receptor expressed on myeloid cells 2 (TREM2) expression on either resident or recruited macrophages is required for the efficient clearance of dying cells, enhancing repair and preventing exacerbated fibrosis.}},
  author       = {{De Ponti, Federico Francesco and Bujko, Anna and Liu, Zhuangzhuang and Collins, Paul and Schuermans, Sara and Maueröder, Christian and Amstelveen, Seraja and Thoné, Tinne and Martens, Liesbet and McKendrick, John and Louwe, Pieter and Sánchez Cruz, Ana and Saelens, Wouter and Matchett, Kylie P. and Waller, Kathryn and Zwicker, Christian and Bugler-Lamb, Aimee-Rose and Vanneste, Bavo and Parmentier, Fleur and Binte Abdul Latib, Mushida and Remmerie, Anneleen and Kertész, Lénárd and Kremer, Anna and Verbeke, Jérémy and Ipsen, David Højland and Pfister, Dominik Reinhard and Liu, Zhaoyuan and Guilliams, Martin and Henderson, Neil C. and Ravichandran, Kodi and Marques, Pedro E. and Scott, Charlotte}},
  issn         = {{1074-7613}},
  journal      = {{IMMUNITY}},
  keywords     = {{KUPFFER CELLS,LIVER,LANDSCAPE,MICROGLIA,TREM2,DEFICIENT,DIVERSITY,BIOLOGY,DRIVES,MODEL}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{362--380}},
  title        = {{Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair}},
  url          = {{http://doi.org/10.1016/j.immuni.2025.01.002}},
  volume       = {{58}},
  year         = {{2025}},
}
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