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Cited by 173Immune Response and InflammationImmunotherapy and Immune ResponsesInflammation biomarkers and pathways

TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells

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Ito, Hiroaki, Hamerman, Jessica A.·2012·European Journal of Immunology
DOI 10.1002/eji.201141679PMC PMC3444819
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Abstract

DCs play a key role in defense against infections and also in preventing inflammatory and autoimmune diseases. The response of DCs to pathogens is tightly regulated by many mechanisms to allow for appropriate, but not pathogenic, responses. We previously showed that DCs with deficiencies for two ITAM‐bearing signaling adapters, DAP12 and FcRγ, produce more inflammatory cytokines upon treatment with Toll‐like receptor (TLR) agonists than WT DCs. Here, we investigated whether the TREM‐2 receptor pairs with DAP12 to inhibit TLR responses in DCs. TREM‐2‐deficient BMDCs showed increased inflammatory cytokine and type I IFN production in response to TLR ligation. Additionally, TREM‐2‐deficient BMDCs had increased TLR‐induced maturation and were more efficient at inducing antigen‐specific T‐cell proliferation upon CpG DNA stimulation compared with WT BMDCs. Finally, we showed that a TREM‐2 ligand is expressed on the surface of BMDCs, suggesting that the TREM‐2 receptor transduces inhibitory signals due to recognition of an endogenous ligand.

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  • Trem2−/− macrophages present antigens to T cells more effectively than WT macrophages in vitro.

    “Trem2−/− macrophages were shown to present antigens to T cells more effectively than WT macrophages in vitro (Ito and Hamerman, 2012).”

    From TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy (2020) · cites this paper as Ito and Hamerman, 2012

    The Results section (“TREM-2 negatively regulates antigen-specific T cell proliferation by BMDCs”; page unavailable) reports that TREM-2-deficient bone-marrow-derived dendritic cells induced more antigen-specific T-cell division than WT dendritic cells in vitro. The cited experiment did not test macrophages, so the claim attributes the finding to the wrong cell type. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • TREM2 activation causes inhibition of the Toll-like-receptor (TLR)-induced proinflammatory cytokine responses in macrophages and dendritic cells.

    “While TREM2 activation causes inhibition of the Toll-like-receptor (TLR)-induced proinflammatory cytokine responses in macrophages and dendritic cells [30]”

    From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [30]

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References 51 · Cited by 173

Research works printed but not linked: 43

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Authors
Ito, H., & Hamerman, J. A.
Affiliations
University of Washington (US)
Corresponding author
Hamerman, Jessica A.
ORCID
Venue
European Journal of Immunology
Publisher
Wiley
Published
2011-12-12
Volume
42
Issue
1
Pages
176-185
ISSN
  • 0014-2980 (ISSN-L)
  • 1521-4141
DOI
10.1002/eji.201141679
PMC
PMC3444819
OpenAlex
W2074800088
Cited by
173
References
51
Citations by year
2026: 5 · 2025: 16 · 2024: 13 · 2023: 7 · 2022: 17 · 2021: 9 · 2020: 15 · 2019: 6 · 2018: 14 · 2017: 15 · 2016: 9 · 2015: 14 · 2014: 15 · 2013: 13 · 2012: 5
FWCI
4.68
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • European Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Cancer Research Institute
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R01AI081948, R01AI073441, AI081948, AI073441)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR055695)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
TREM2, dendritic cells, Toll-like receptor signaling, DAP12, inhibitory signaling, type I interferon, inflammatory cytokines, dendritic cell maturation, T cell proliferation, CpG DNA, myeloid cells
MeSH terms
Animals, Dendritic Cells, Flow Cytometry, Lymphocyte Activation, Membrane Glycoproteins, Mice, Inbred C57BL, Receptors, Immunologic, RNA, Specific Pathogen-Free Organisms, Signal Transduction, Cytokines, Mice, Knockout, CpG Islands, Reverse Transcriptase Polymerase Chain Reaction, Myeloid Cells, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, Mice

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