[NTR] lipid-associated macrophage

[EMRutherford]

Preferred term label lipid-associated macrophage

Synonyms (add reference(s), please) LAM

Definition (free text, with reference(s), please. PubMed ID format is PMID:XXXXXX) Macrophages associated with lipids in adipose tissue and around bile ducts and in steatotic regions of the liver. Expresses Trem2.
Marker genes include Lipa, Lpl, Ctsb, Ctsl, Fabp4, Fabp5, Lgals1, Lgals3, Cd9, Lgmn, Gpmnb, Spp1, and Cd36.

Parent cell type term (check the hierarchy here https://www.ebi.ac.uk/ols4/ontologies/cl) tissue-resident macrophage (CL:0000091)

Anatomical structure where the cell type is found (check Uberon for anatomical structures: https://www.ebi.ac.uk/ols4/ontologies/uberon) liver (UBERON:0002107); adipose tissue (UBERON:0001013)

References

• Jaitin et al. 2019 (“Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner”, DOI:10.1016/j.cell.2019.05.054, PMID:31257031)

• Guilliams et al. 2022 (“Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches”, DOI: https://doi.org/10.1016/j.cell.2021.12.018, PMID:35021063)

• Li et al 2023 (“Adipose tissue macrophages as potential targets for obesity and metabolic diseases”, DOI:10.3389/fimmu.2023.1153915, PMID:37153549)

• Remmerie et al. 2020 (“Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver”, DOI: 10.1016/j.immuni.2020.08.004, PMID: 32888418)

• Eraslan et al. 2022 (“Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function”, DOI: 10.1126/science.abl4290, PMID: 35549429)

Your ORCID 0000-0001-8134-3037

Additional notes or concerns Distinct from “adipose macrophage” in Trem2 expression, and is not limited to adipose tissue. Guilliams et al. describe these cells as being distinct from Kupffer cells: “LAMs expressed more Il1b at steady state compared with KCs (Figure 2L). However, despite this, upon in vivo TLR4 stimulation, they were less responsive than KCs, both in terms of pro- and anti-inflammatory cytokines (Figure 2L), possibly indicative of LPS tolerance.”

[emquardokus]

Dib, L., Koneva, L.A., Edsfeldt, A. et al. Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications. Nat Cardiovasc Res 2, 656–672 (2023). https://doi.org/10.1038/s44161-023-00295-x

[dosumis]

Discussion from CL call:

• We need more details on distinct function and location(s) and on what distinguished from similar macrophages.
• Need to be careful about relying on species specific markers - if formally recorded, these need to be in an axiom that references species specificity.

Any evidence for functional distinction?

• Some evidence that they participate in lipid metabolism.

[emquardokus]

Has mouse and human: Li, Xirong, Yakun Ren, Kewei Chang, Wenlong Wu, Helen R. Griffiths, Shemin Lu, and Dan Gao. 2023. “Adipose Tissue Macrophages as Potential Targets for Obesity and Metabolic Diseases.” Frontiers in Immunology 14. https://www.frontiersin.org/articles/10.3389/fimmu.2023.1153915.

[aleixpuigb]

Hi @EMRutherford, thank you for your request. If possible, I would like to ask for some clarifications on these term. This term is found not only in the liver, but also in the bile duct (mentioned in the textual definition) and in other tissues, (e.g. subcutaneous adipose tissue depots) (Jacks and Lumeng, 2023). Is the term requested specific for the liver? The term requested is Trem2+, but there is at least another subset/cluster Trem1+ Plin2+ LAM (Dib et al., 2023). Are you requesting only the Trem2+ LAM? If both answers are yes, I would recommend calling the therm 'hepatic Trem2+ lipid-associated macrophage'. However, I would advise to create three terms that are not specific for the liver: A grouping lipid-associated macrophage, with 2 subclasses (Trem2+ LAM and Plin2+Trem1+ LAM).

[EMRutherford]

Hi @aleixpuigb , (sorry about the delayed response), I was doing some thinking and reading about this issue. The term that I requested was not meant to be specific to the liver, although I was requesting it for a liver dataset. Your suggestion of the term "lipid-associated macrophage" with the two subterms would work for my use case.

However, when reading the paper mentioned (Dib et al., 2023), I noticed that the Trem1+ Plin2+ LAMs appear to be an activated, inflammatory cell state that is terminally differentiated from Trem2+ LAMs rather than a completely different cell type. I'm not sure how CL handles these cases - I was under the impression that cell states are not typically given their own CL term. Here are some relevant statements from the paper:

• "The apparent absence of an obvious murine macrophage phenotype similar to that of human PLIN2hi/TREM1hi LAMs (Supplementary Fig. 3h) suggests that there may be a divergent division of labor between monocytes and macrophages or that the duration of current mouse models may not be sufficient to reproduce this feature of human disease."
• "This analysis confirmed that the PLIN2hi/TREM1hi subset was the only one in the plaque to simultaneously display signatures of lipid handling, inflammation and apoptosis, suggesting that they represented a terminal inflammatory LAM state"
• "Consistent with the RNA-velocity results, random walk analysis (CellRank, CytoTRACE kernel) also predicted that TREM2hi could differentiate into inflammatory PLIN2hi/TREM1hi LAMs (Fig. 3e,f) but did not provide support for differentiation in the opposite direction"