Affinage

CD300LF

CMRF35-like molecule 1 · UniProt Q8TDQ1

Length
290 aa
Mass
32.3 kDa
Annotated
2026-04-28
60 papers in source corpus 31 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD300LF (CD300f/CLM-1/LMIR3/IREM-1) is a myeloid-lineage immunomodulatory receptor whose extracellular Ig-V domain engages phosphatidylserine and ceramide on apoptotic or activated cells, and whose cytoplasmic tail integrates inhibitory and activating signals to govern innate immune effector functions, efferocytosis, and pathogen entry. Its tandem ITIMs (Y205, Y249 in human) recruit SHP-1 and SHP-2 to suppress FcεRI, TLR/MyD88/TRIF–NF-κB, and STING signaling cascades, dampening mast cell degranulation, eosinophil chemotaxis, neutrophil antimicrobial activity, and neuroinflammation (PMID:15549731, PMID:21536801, PMID:22043923, PMID:23820751, PMID:30479367, PMID:38965803); a distinct PI3K-binding motif (Y236/Y263 human; Y276 mouse) recruits p85α to activate Rac/Cdc42-driven actin remodeling for phagocytic cup formation, and this pathway also drives PD-L1 upregulation and M2 macrophage polarization (PMID:17202342, PMID:24477292, PMID:37302321). The balance between inhibitory and activating outputs is cell-type-dependent—macrophages and microglia require CD300f for efficient efferocytosis and damage sensing, whereas in dendritic cells it restrains apoptotic cell uptake, and its loss leads to lupus-like autoimmunity or exacerbated colitis (PMID:24477292, PMID:28414292, PMID:26768664, PMID:40935207). In mice, CD300lf also serves as the sole physiological receptor for murine norovirus, binding the viral P domain in a structurally defined 2:2 complex through its CC' loop, with bile acids acting as cofactors; CD300lf-deficient mice are fully resistant to MNoV infection (PMID:27681626, PMID:30194229, PMID:32251490, PMID:32581099).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2004 High

    Establishing CD300f as an ITIM-bearing inhibitory receptor resolved how this orphan immunoglobulin superfamily member transduces signals, identifying SHP-1 recruitment via phospho-Y205 and functional suppression of FcεRI activation.

    Evidence Yeast three-hybrid screen, co-IP, Y205 mutagenesis, and degranulation assay in myeloid cells

    PMID:15549731

    Open questions at the time
    • SHP-2 recruitment not yet tested
    • Endogenous ligand unknown
    • In vivo relevance of FcεRI inhibition not assessed
  2. 2007 High

    Demonstrating that distinct cytoplasmic tyrosines mediate opposing signals—ITIMs for inhibition via SHP-1 and non-ITIM tyrosines for activation via PI3K p85α—established CD300f as a dual-function signaling receptor whose output depends on which motifs are engaged.

    Evidence Systematic tyrosine mutants in transfected cells and U937 monocytes; co-IP of p85α; PI3K inhibitor experiments; crystal structure of the Ig-V domain at 2.6 Å

    PMID:17202342 PMID:17275839 PMID:17329815

    Open questions at the time
    • No endogenous ligand identified
    • Structural basis of ligand binding not resolved
    • Cell-type-specific signaling balance unexplored
  3. 2009 High

    Defining CD300f as a negative regulator of myeloid effector responses in autoimmune demyelination established its in vivo immunosuppressive role, showing that loss increases NO and pro-inflammatory cytokines without affecting T cell priming.

    Evidence CLM-1-deficient mice in MOG-EAE model with cytokine, NO, and T cell analysis

    PMID:20038601

    Open questions at the time
    • Ligand driving inhibition in EAE not identified
    • Downstream signaling pathway in CNS myeloid cells not mapped
    • Contribution of individual signaling motifs unknown
  4. 2011 High

    Identification of phosphatidylserine as the extracellular ligand, together with mapping CD300f's inhibitory action to both MyD88- and TRIF-dependent TLR pathways via SHP-1/NF-κB suppression, connected ligand recognition to a defined signaling cascade for the first time.

    Evidence SPR, cosedimentation, and ELISA with PS-containing liposomes; antibody crosslinking and ITIM peptides with NF-κB reporter, IKK/IκB Western blots, and SHP-1 inhibitors in monocytic cells

    PMID:21536801 PMID:21865548

    Open questions at the time
    • Ceramide binding not yet recognized
    • Whether PS engagement drives inhibitory or activating arm not distinguished
    • In vivo relevance of PS-driven TLR inhibition not tested
  5. 2013 High

    Showing that PS–CD300f engagement suppresses eosinophil chemotaxis, actin polymerization, and ERK signaling extended the receptor's inhibitory function beyond mast cells and macrophages to granulocyte migration.

    Evidence Clm1-/- mice with baseline eosinophilia; in vitro chemotaxis, Ca²⁺ flux, ERK assays; PS liposome treatment; allergic airway model

    PMID:23820751

    Open questions at the time
    • Whether inhibition is SHP-1- or SHP-2-dependent in eosinophils not tested
    • Contribution of ceramide not assessed
  6. 2014 High

    Demonstrating that CD300f accumulates in phagocytic cups and that Y276-p85α-Rac/Cdc42-F-actin signaling drives apoptotic cell engulfment resolved how the activating arm operates mechanistically; CD300f-KO mice developing lupus-like disease established efferocytosis failure as a disease-relevant consequence.

    Evidence Confocal imaging, phosphotyrosine mutants, co-IP of p85α, Rac/Cdc42 GTPase assays, and CD300f-KO/FcγRIIB-KO mice

    PMID:24477292

    Open questions at the time
    • How inhibitory and activating arms are balanced in the same cell not resolved
    • Whether lupus phenotype maps to macrophage or DC efferocytosis defect unknown
  7. 2015 High

    Identification of ceramide as a second lipid ligand, and demonstration that ceramide–CD300f interaction inhibits ATP/P2X7-mediated mast cell activation and suppresses colitis, revealed a distinct anti-inflammatory axis beyond PS recognition; separately, physical association with IL-4Rα showed CD300f amplifies type-2 cytokine signaling.

    Evidence LMIR3-/- and mast-cell-deficient mice with BMMC reconstitution; ceramide liposomes in DSS colitis; co-IP of CD300f/IL-4Rα; allergen challenge in Cd300f-/- mice

    PMID:25673319 PMID:26124135

    Open questions at the time
    • Structural basis of ceramide vs PS selectivity unknown
    • Whether IL-4Rα association requires PS/ceramide engagement untested
    • Relative contribution of PS and ceramide in vivo unclear
  8. 2016 High

    Discovery that CD300f promotes efferocytosis in macrophages but inhibits it in dendritic cells resolved the apparent paradox of pro- vs anti-inflammatory KO phenotypes, establishing cell-type context as the critical determinant of receptor output; simultaneously, CD300lf was identified as the entry receptor for murine norovirus by genome-wide CRISPR screen.

    Evidence Cell-type-specific phagocytosis assays in CD300f-KO mice with colitis/autoimmunity models; CRISPR screen with gain-of-function and antibody blockade for MNoV

    PMID:26768664 PMID:27681626 PMID:28414292

    Open questions at the time
    • Molecular mechanism of cell-type-specific signaling not identified
    • Post-entry steps of MNoV infection through CD300lf unknown
    • Whether human CD300f shares DC-specific inhibitory function untested
  9. 2017 High

    Extension of the ceramide–CD300f inhibitory axis to neutrophils and mast cells in skin inflammation and sepsis demonstrated that disrupting this interaction could be either harmful (exacerbating inflammation) or beneficial (enhancing bacterial clearance), revealing context-dependent therapeutic implications.

    Evidence CD300f-/- and mast-cell-deficient mice with BMMC reconstitution and adoptive neutrophil transfer; ceramide vesicle and anti-ceramide antibody in LPS skin and CLP sepsis models

    PMID:28073916 PMID:28655892

    Open questions at the time
    • How ceramide release is regulated during infection not addressed
    • Ceramide species specificity not resolved
  10. 2018 High

    Atomic-resolution crystal structure of CD300lf bound to the MNoV P domain defined the 2:2 binding stoichiometry, identified the CC' and DE loop interface overlapping neutralizing epitopes, revealed metal-coordinated mimicry of phosphocholine binding, and showed bile acids act as cofactors at a distinct site.

    Evidence X-ray crystallography at 2.05 Å; SPR and ITC; interface mutagenesis; co-crystallization with bile acids GCDCA and LCA

    PMID:29563286 PMID:30194229

    Open questions at the time
    • Structural basis of ceramide binding to CD300f not determined
    • How bile acid cofactor activity operates mechanistically in vivo not fully resolved
  11. 2020 High

    Genetic proof that CD300lf is the sole physiologic MNoV receptor in vivo was established by complete resistance of CD300lf-KO mice to oral and parenteral infection; CC' loop polymorphisms between mouse strains were shown to determine receptor function in a cell-type-dependent manner; a human CD300f variant (rs2034310) affecting PKC phosphorylation was linked to major depressive disorder and microglial metabolic fitness.

    Evidence CD300lf global KO mice with oral/parenteral MNoV; chimeric CD300lf domain-swap mutagenesis across inbred strains; human GWAS with PKC phosphorylation analysis and CD300f-KO mouse behavioral/metabolic phenotyping

    PMID:32152116 PMID:32251490 PMID:32581099

    Open questions at the time
    • Human CD300f does not serve as human norovirus receptor—human norovirus receptor identity remains open
    • How PKC phosphorylation of CD300f regulates microglial metabolism mechanistically unknown
    • Cell-type determinants of CC' loop polymorphism sensitivity not identified
  12. 2021 High

    Conditional KO studies pinpointed intestinal tuft cells as the CD300lf-expressing cells essential for persistent MNoV transmission and myelomonocytic cells as primary targets for acute strains, establishing cell-type-specific tropism determinants.

    Evidence Conditional CD300lf KO with Villin-Cre, DCLK1-Cre, LysM-Cre, and other Cre drivers; in vivo infection with qRT-PCR viral load

    PMID:33177207

    Open questions at the time
    • What determines CD300lf expression levels in tuft cells vs myeloid cells unknown
    • Post-entry replication steps in tuft cells not characterized
  13. 2024 Medium

    Identification of STING signaling as a downstream pathway inhibited by CD300LF in microglia after traumatic brain injury provided a new mechanistic link between CD300f and innate nucleic acid sensing in the CNS.

    Evidence CD300LF-KO mice in TBI model; transcriptomic comparison; STING inhibitor (C-176) rescue of neurological deficits

    PMID:38965803

    Open questions at the time
    • Direct biochemical connection between CD300f ITIM signaling and STING pathway not demonstrated
    • Whether SHP-1/SHP-2 mediate STING suppression not tested
    • Single lab finding
  14. 2025 High

    Intravital imaging and proteomics in CD300f-KO mice revealed that CD300f is required for microglial damage sensing, process extension, apoptotic cell recognition, and phagolysosomal processing, with disrupted purinergic (UDP-P2RY6) signaling as an underlying mechanism; separately, CD300f and CD300a were shown to cooperate in inhibiting mast cell activation, with ceramide producing stronger inhibition than PS; and CD300f was identified as a macrophage receptor exploited by Rickettsia species via bacterial PS.

    Evidence Two-photon intravital microscopy with mTBI and apoptotic cell injection models; proteomics and RT-PCR; double-KO (Cd300a/Cd300lf) mice in anaphylaxis; CD300f-KO macrophages with Rickettsia infection and adoptive transfer

    PMID:40073110 PMID:40310290 PMID:40935207

    Open questions at the time
    • Whether purinergic signaling disruption is a direct consequence of CD300f loss or secondary to metabolic changes is unclear
    • Structural basis of cooperative CD300a/CD300f signaling unknown
    • Whether Rickettsia PS exposure is an active immune evasion strategy not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for ceramide versus PS discrimination by CD300f; the molecular mechanism underlying opposite efferocytosis outcomes in macrophages versus dendritic cells; whether the CD300f-STING and CD300f-purinergic axes represent direct signaling connections or indirect consequences; and identification of the human norovirus receptor.
  • No co-crystal structure with ceramide
  • No cell-type-specific signaling complex characterized
  • Human norovirus receptor unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0001618 virus receptor activity 3 GO:0008289 lipid binding 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 1
Partners
CD300AIL4RPIK3R1SHP-1SHP-2

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 CD300f (mouse CD300f/LMIR3) binds phosphatidylserine (PS) exposed on the outer membrane of apoptotic cells, requiring a metal ion, and ectopic CD300f expression enhances phagocytosis of apoptotic cells by myeloid cells. ELISA, cosedimentation, surface plasmon resonance with phospholipid-containing liposomes; Annexin V competition; flow cytometry phagocytosis assay Journal of immunology High 21865548
2004 IREM-1 (human CD300f ortholog) recruits SHP-1 via its cytoplasmic ITIM, with phosphotyrosine Y205 as the primary docking site, and cross-linking IREM-1 inhibits FcεRI-induced activation in myeloid cells. Yeast three-hybrid screen; Western blot; immunoprecipitation; Y205 mutagenesis; functional degranulation assay European journal of immunology High 15549731
2007 CD300f (IREM-1) cytoplasmic domain recruits both p85α (PI3K regulatory subunit) and SHP-1; ITIMs Y205 and Y249 are required for inhibitory function, while Y236 and Y263 mediate PI3K recruitment and can drive activating signals when ITIMs are mutated. Immunoprecipitation in transfected cells and U937 monocytic cells; IREM-1 tyrosine mutants; RBL cell degranulation assay; PI3K inhibitors (wortmannin, LY-294002) Journal of immunology High 17202342
2007 Crystal structure of the IREM-1 (human CD300f) extracellular Ig-V domain determined at 2.6 Å; CDR3-equivalent loop identified as the structurally variable region likely mediating ligand discrimination; three cavities form a continuous hydrophobic groove as a potential ligand-binding surface. X-ray crystallography (2.6 Å resolution); structural comparison with CLM-1, TREM-1, TLT-1, NKp44 Journal of molecular biology High 17275839 17329815
2014 CD300f accumulates in phagocytic cups at apoptotic cell contact sites; phosphorylation of Y276 in the cytoplasmic tail recruits p85α (PI3K regulatory subunit), activating Rac/Cdc42 GTPases and driving F-actin remodeling required for apoptotic cell engulfment; CD300f-deficient macrophages show impaired efferocytosis and CD300f-deficient mice develop lupus-like autoimmunity. Confocal microscopy (phagocytic cup localization); phosphotyrosine mutants; co-immunoprecipitation of p85α; Rac/Cdc42 activation assay; F-actin staining; CD300f-KO mouse phenotype with FcγRIIB-KO cross Nature communications High 24477292
2016 CD300f and CD300ld function as murine norovirus (MNoV) cell-surface receptors; ectopic CD300lf expression in non-susceptible cell lines confers MNoV permissibility; anti-CD300lf antibody blocks viral progeny production. Genome-wide CRISPR/Cas9 screen; ectopic expression in non-susceptible cell lines; antibody blocking assay; progeny virus quantification Proceedings of the National Academy of Sciences of the United States of America High 27681626
2018 Crystal structure of soluble CD300lf in complex with the MNoV VP1 protruding (P) domain determined at 2.05 Å; CD300lf binds with 2:2 stoichiometry at a cleft between AB and DE loops of P2 subdomain overlapping neutralizing antibody epitopes; engagement mimics host phosphocholine ligand binding including metal coordination; bile acids bind at a separate site on the P domain dimer interface and act as cofactors. X-ray crystallography (2.05 Å); biophysical assays (SPR, ITC); interface residue mutagenesis; cryo-EM docking; co-crystallization with bile acids GCDCA and LCA Proceedings of the National Academy of Sciences of the United States of America High 29563286 30194229
2020 CD300lf is the essential physiologic receptor for MNoV in vivo; CD300lf-deficient mice are fully resistant to both oral and parenteral MNoV infection and fail to mount anti-MNoV humoral responses; human CD300lf does not serve as a receptor for human norovirus. CD300lf global knockout mice; oral and parenteral infection models; STAT1-deficient/CD300lf-deficient cross; huCD300lf overexpression in cell culture with HNoV VLPs PLoS pathogens High 32251490
2021 CD300lf expression on intestinal tuft cells is essential for persistent MNoV (CR6) transmission in vivo; myelomonocytic cells are the primary but not exclusive target cells for non-persistent MNoV (CW3); STAT1 signaling restricts MNoV cell tropism independently of LysM+ CD300lf expression. Conditional CD300lf knockout mice using cell-type-specific Cre drivers (Villin, DCLK1, LysM, CD19, Mrp8, CD11c); in vivo infection with quantitative RT-PCR for viral load Journal of virology High 33177207
2009 CLM-1 (mouse CD300f ortholog) acts as a negative regulator of myeloid effector cell activity in autoimmune demyelination; CLM-1 deficiency increases nitric oxide and pro-inflammatory cytokine production and worsens EAE clinical scores without affecting peripheral T cell responses. CLM-1-deficient mice in MOG35-55 EAE model; cytokine/NO measurement; T cell response analysis; immunohistochemistry The Journal of experimental medicine High 20038601
2011 CD300F inhibits both MyD88- and TRIF-mediated TLR signaling in human monocytic cells through SHP-1 activation, suppressing IκBα kinase activation, IκB phosphorylation/degradation, and NF-κB activation. Anti-CD300F mAb crosslinking and ITIM synthetic peptides; luciferase NF-κB reporter in 293T cells; Western blot for IKK/IκB/NF-κB; SHP-1 inhibitors; immunoprecipitation Journal of immunology High 21536801
2015 CD300f is co-localized and physically associated with IL-4Rα on myeloid cells; CD300f amplifies IL-4Rα-induced signaling, mediator release, and priming; Cd300f-deficient mice show decreased IgE production and reduced airway inflammation after allergen challenge. Co-immunoprecipitation; colocalization microscopy; receptor cross-linking; Cd300f-/- mice in allergen model with cytokine and IgE measurements Proceedings of the National Academy of Sciences of the United States of America High 26124135
2015 Ceramide binding to CD300f (LMIR3) inhibits ATP/P2X7-mediated mast cell activation; LMIR3 deficiency exacerbates DSS-induced colitis in a mast cell-dependent manner; ceramide liposomes suppress colitis through ceramide-LMIR3 interaction. LMIR3-/- mice; mast cell-deficient mice with WT or LMIR3-/- BMMC reconstitution; ELISA for mediators from ATP-stimulated BMMCs ± ceramide; ceramide liposome/anti-ceramide antibody administration in colitis model Gut High 25673319
2013 CLM-1 (CD300f) negatively regulates eotaxin-induced eosinophil chemotaxis, actin polymerization, calcium influx, and ERK1/2 phosphorylation; phosphatidylserine engagement of CLM-1 renders eosinophils hypochemotactic in vitro and in vivo. Clm1-/- mice (baseline eosinophilia phenotype); in vitro chemotaxis, actin polymerization, calcium flux, ERK phosphorylation assays; PS liposome treatment; CLM-1 blocking in allergic airway disease model Mucosal immunology High 23820751
2016 In dendritic cells (DCs), CD300f expression inhibits efferocytosis; CD300f-deficient DCs display hyperactive phagocytosis of apoptotic cells, stimulating excessive TNF-α secretion that drives secondary IFN-γ production by colonic T cells and prolonged gut inflammation. CD300f-KO mice in DSS colitis model; DC-specific phagocytosis assay; TNF-α and IFN-γ measurements; apoptotic cell accumulation in gut The Journal of clinical investigation High 28414292
2016 CD300f function in macrophages (promotes efferocytosis) is opposite to its function in dendritic cells (inhibits efferocytosis); CD300f deficiency in DCs leads to enhanced antigen processing, T cell priming, and expansion of memory T cells predisposing to autoimmunity. CD300f-KO mice; cell-type-specific efferocytosis assays; T cell priming and ANA measurements in aged mice; apoptotic cell overload and FcγRIIB-deficiency cross Cell death and differentiation Medium 26768664
2008 Cross-linking CD300LF (MAIR-V) induces caspase-independent, ER-stress-independent cell death in peritoneal macrophages and transfectants; cell death requires the cytoplasmic region but not the ITIM or ITSM motifs. Anti-CD300LF mAb crosslinking; caspase inhibitor (z-VAD-fmk); autophagy inhibitors; ER stress marker (XBP-1 splicing); scanning electron microscopy; cytoplasmic domain deletion mutants Journal of immunology Medium 18097021
2012 CD300a blocks only MyD88-mediated TLR signaling via SHP-1, whereas CD300f blocks both MyD88- and TRIF-mediated TLR signaling through combined activation of SHP-1 and SHP-2. TLR ligand stimulation of THP-1 and U937 cells; ITIM synthetic peptides; luciferase reporter (NF-κB); Western blot; signaling inhibitors Immunology Medium 22043923
2004 IgSF13 (human CD300f-related protein encoded on chromosome 17q25.2) upon pervanadate treatment is hyper-phosphorylated and recruits SHP-1 and SHIP (but not SHP-2) via its ITIMs. Pervanadate treatment; co-immunoprecipitation; Western blot Biochemical and biophysical research communications Low 15184070
2017 Ceramide binding to CD300f suppresses LPS-induced mast cell and neutrophil mediator release, reducing skin edema and neutrophil recruitment in vivo; disrupting ceramide-CD300f interaction exacerbates LPS-induced skin inflammation. CD300f-/- mice; mast cell-deficient mice with BMMC reconstitution; adoptive neutrophil transfer; ceramide antibody and ceramide vesicle administration; mediator ELISA The Journal of biological chemistry High 28073916
2017 Ceramide-CD300f interaction inhibits ATP-stimulated mast cell neutrophil chemoattractant production; disrupting this interaction in a CLP sepsis model augments neutrophil recruitment and bacterial clearance, protecting from septic death. CD300f-/- mice; mast cell-deficient mice with WT or CD300f-/- BMMC transfer; CLP model; ceramide vesicle/anti-ceramide antibody administration; ELISA for chemoattractants and bacterial colony counts Scientific reports High 28655892
2018 LMIR3/CD300f negatively regulates neutrophil antimicrobial activity; LMIR3-KO neutrophils show increased hypochlorous acid production, elastase release, and cytotoxic activity against P. aeruginosa and C. albicans; LMIR3 expression on neutrophils increases in response to P. aeruginosa infection in a TLR4/MyD88-dependent manner. LMIR3-KO mice; in vitro neutrophil killing assays; elastase/myeloperoxidase inhibitors; in vivo Pseudomonas peritonitis and systemic candidiasis models Scientific reports Medium 30479367
2023 CD300f signaling in human monocytes activates the PI3K/Akt pathway, upregulates PD-L1 (CD274), and promotes M2-type macrophage polarization; PI3K/Akt inhibition abrogates CD300f-driven PD-L1 upregulation. Anti-CD300f mAb (DCR-2) crosslinking; flow cytometry; PI3K/Akt inhibitors; T cell proliferation suppression assay; M1/M2 polarization markers Cellular immunology Medium 37302321
2025 CD300f on macrophages mediates engulfment of Rickettsia species by recognizing bacterial phosphatidylserine as ligand; CD300f-/- macrophages show reduced engulfment of R. typhi, R. rickettsii, and R. montanensis; CD300f-/- mice are protected from lethal rickettsiosis. CD300f-/- bone marrow-derived macrophages; in vivo infection of WT and KO mice; adoptive transfer of CD300f-expressing macrophages; bacterial burden quantification Infection and immunity High 40310290
2025 CD300lf and CD300a cooperate to inhibit FcεRI-mediated mast cell activation; both receptors co-localize with PS externalized to the outer leaflet upon activation; CD300lf binding to extracellular ceramide produces stronger MC inhibition than PS binding alone; double-KO mice show more severe anaphylaxis than single KOs. Imaging and flow cytometry of BMMCs from WT, Cd300a-/-, Cd300lf-/-, Cd300a-/-Cd300lf-/- mice; passive systemic anaphylaxis model; colocalization with PS and ceramide Journal of immunology High 40073110
2025 CD300f-deficient microglia fail to extend processes toward laser-induced cortical lesions (impaired damage sensing); show reduced recognition and clearance of apoptotic cells; retain apoptotic remnants indicating defective phagolysosomal processing; proteomic analysis reveals dysregulation of autophagy-related and metabolic pathways; ENTPD6 upregulation and P2ry6 mRNA downregulation suggest disrupted UDP-P2RY6 purinergic signaling axis underlying impaired phagocytic initiation. Intravital two-photon microscopy; CD300f-/- mice; mTBI and intracortical apoptotic cell injection models; controlled cortical injury contusion model; proteomics; RT-PCR; in vitro BMDM phagolysosomal assay Brain, behavior, and immunity High 40935207
2020 A nonsynonymous SNP (rs2034310, C/T) in the human CD300f cytoplasmic tail inhibits protein kinase C phosphorylation of a threonine residue and is associated with protection against major depressive disorder; CD300f-/- mice display impaired microglial metabolic fitness and depressive/anhedonic behaviors in females. Human genetic association (rs2034310); PKC phosphorylation site analysis; CD300f-/- mouse behavioral phenotyping; RNA sequencing and biochemical metabolic studies of microglia Proceedings of the National Academy of Sciences of the United States of America Medium 32152116
2024 CD300LF-positive microglia impede neuroinflammation after traumatic brain injury principally by inhibiting the STING signaling pathway; CD300LF-deficient mice show increased glial proliferation, greater neuronal loss, and worse neurological function post-TBI. CD300LF-deficient mice; TBI model; transcriptomic comparison between CD300LF+ and CD300LF- microglia; STING pathway inhibitor (C-176) rescue CNS neuroscience & therapeutics Medium 38965803
2020 Polymorphisms in the CD300LF CC' loop (4-amino-acid difference between C57BL/6J and I/LnJ strains) determine MNoV receptor function in a cell-type-dependent manner; I/LnJ CD300LF does not function as MNoV receptor in macrophage-like cells but supports infection in other cell types. Bone marrow-derived macrophages from multiple inbred mouse strains; transduction with chimeric CD300LF constructs; virus binding assay; site-directed mutagenesis of CC' loop residues Journal of virology High 32581099

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells. Proceedings of the National Academy of Sciences of the United States of America 145 27681626
2018 Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor. Proceedings of the National Academy of Sciences of the United States of America 92 30194229
2011 Cutting edge: mouse CD300f (CMRF-35-like molecule-1) recognizes outer membrane-exposed phosphatidylserine and can promote phagocytosis. Journal of immunology (Baltimore, Md. : 1950) 81 21865548
2014 p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression. Nature communications 78 24477292
2004 IREM-1 is a novel inhibitory receptor expressed by myeloid cells. European journal of immunology 66 15549731
2020 CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus. PLoS pathogens 63 32251490
2009 CLM1 of Fusarium graminearum encodes a longiborneol synthase required for culmorin production. Applied and environmental microbiology 61 19880637
2015 Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation. Gut 55 25673319
2015 CD300f associates with IL-4 receptor α and amplifies IL-4-induced immune cell responses. Proceedings of the National Academy of Sciences of the United States of America 55 26124135
2007 Expression, crystallization and X-ray data collection from microcrystals of the extracellular domain of the human inhibitory receptor expressed on myeloid cells IREM-1. Acta crystallographica. Section F, Structural biology and crystallization communications 54 17329815
2007 The IREM-1 (CD300f) inhibitory receptor associates with the p85alpha subunit of phosphoinositide 3-kinase. Journal of immunology (Baltimore, Md. : 1950) 53 17202342
2009 Negative regulation of autoimmune demyelination by the inhibitory receptor CLM-1. The Journal of experimental medicine 52 20038601
2012 CD300a and CD300f differentially regulate the MyD88 and TRIF-mediated TLR signalling pathways through activation of SHP-1 and/or SHP-2 in human monocytic cell lines. Immunology 45 22043923
2011 CD300F blocks both MyD88 and TRIF-mediated TLR signaling through activation of Src homology region 2 domain-containing phosphatase 1. Journal of immunology (Baltimore, Md. : 1950) 43 21536801
2015 CD300f immunoreceptor contributes to peripheral nerve regeneration by the modulation of macrophage inflammatory phenotype. Journal of neuroinflammation 40 26259611
2017 Ceramide-CD300f Binding Inhibits Lipopolysaccharide-induced Skin Inflammation. The Journal of biological chemistry 34 28073916
2016 Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice. Cell death and differentiation 34 26768664
2018 Atomic Structure of the Murine Norovirus Protruding Domain and Soluble CD300lf Receptor Complex. Journal of virology 32 29563286
2013 CMRF35-like molecule 1 (CLM-1) regulates eosinophil homeostasis by suppressing cellular chemotaxis. Mucosal immunology 32 23820751
2020 CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness. Proceedings of the National Academy of Sciences of the United States of America 29 32152116
2017 Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment. Scientific reports 29 28655892
2011 Overexpression of the immunoreceptor CD300f has a neuroprotective role in a model of acute brain injury. Brain pathology (Zurich, Switzerland) 29 21951326
2008 Caspase-independent cell death by CD300LF (MAIR-V), an inhibitory immunoglobulin-like receptor on myeloid cells. Journal of immunology (Baltimore, Md. : 1950) 28 18097021
2007 The crystal structure of the extracellular domain of the inhibitor receptor expressed on myeloid cells IREM-1. Journal of molecular biology 28 17275839
2021 CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus. Journal of virology 26 33177207
2017 Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation. The Journal of clinical investigation 25 28414292
2016 A key requirement for CD300f in innate immune responses of eosinophils in colitis. Mucosal immunology 25 27118491
2017 CD300f:IL-5 cross-talk inhibits adipose tissue eosinophil homing and subsequent IL-4 production. Scientific reports 23 28725048
2009 Monoclonal antibodies against IREM-1: potential for targeted therapy of AML. Leukemia 21 19440216
2004 IgSF13, a novel human inhibitory receptor of the immunoglobulin superfamily, is preferentially expressed in dendritic cells and monocytes. Biochemical and biophysical research communications 20 15184070
2021 CD300a and CD300f molecules regulate the function of leukocytes. International immunopharmacology 19 33548578
2019 Expression of CD300lf by microglia contributes to resistance to cerebral malaria by impeding the neuroinflammation. Genes and immunity 16 31501529
2024 CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway. CNS neuroscience & therapeutics 13 38965803
2015 The Receptor CMRF35-Like Molecule-1 (CLM-1) Enhances the Production of LPS-Induced Pro-Inflammatory Mediators during Microglial Activation. PloS one 13 25927603
2010 Immune receptor expressed on myeloid cells 1 (IREM-1) inhibits B cell activation factor (BAFF)-mediated inflammatory regulation of THP-1 cells through modulation of the activities of extracellular regulated kinase (ERK). Clinical and experimental immunology 13 20646006
2017 Effect of Specific Mutations in Cd300 Complexes Formation; Potential Implication of Cd300f in Multiple Sclerosis. Scientific reports 12 29051512
2012 Synthetic peptides containing ITIM-like sequences of IREM-1 (CD300F) differentially regulate MyD88 and TRIF-mediated TLR signalling through activation of SHP and/or PI3K. Clinical and experimental immunology 12 22288587
2023 CD300f immune receptor contributes to healthy aging by regulating inflammaging, metabolism, and cognitive decline. Cell reports 11 37864797
2022 Dehydroandrographolide targets CD300f and negatively regulated MRGPRX2-induced pseudo-allergic reaction. Phytotherapy research : PTR 11 35312106
2020 Targeting CD300f to enhance hematopoietic stem cell transplantation in acute myeloid leukemia. Blood advances 11 32215656
2018 Mouse LIMR3/CD300f is a negative regulator of the antimicrobial activity of neutrophils. Scientific reports 10 30479367
2022 Clarithromycin-treated chronic spontaneous urticaria with the negative regulation of FcεRΙ and MRGPRX2 activation via CD300f. International immunopharmacology 9 35853276
2023 Microglial CD300f immune receptor contributes to the maintenance of neuron viability in vitro and after a penetrating brain injury. Scientific reports 8 37798310
2019 CD300f epitopes are specific targets for acute myeloid leukemia with monocytic differentiation. Molecular oncology 8 31338922
2011 Synthetic peptides containing ITIM-like sequences of IREM-1 inhibit BAFF-mediated regulation of interleukin-8 expression and phagocytosis through SHP-1 and/or PI3K. Immunology 7 21896016
2008 Expression of a splicing isoform of MAIR-V (CD300LF), an inhibitory immunoglobulin-like receptor on myeloid cells. Hybridoma (2005) 6 18294079
2023 Myricetin served as antagonist for negatively regulate MRGPRX2 mediated pseudo-allergic reactions through CD300f/SHP1/SHP2 phosphorylation. International immunopharmacology 5 36958208
2023 CD300f signalling induces inhibitory human monocytes/macrophages. Cellular immunology 5 37302321
2020 Sex-dependent role of CD300f immune receptor in generalized anxiety disorder. Brain, behavior, & immunity - health 4 34589728
2024 Intranasal administration of ceramide liposome suppresses allergic rhinitis by targeting CD300f in murine models. Scientific reports 3 38600251
2022 The interaction of CD300lf and ceramide reduces the development of periodontitis by inhibiting osteoclast differentiation. Journal of clinical periodontology 3 36089906
2020 CD300LF Polymorphisms of Inbred Mouse Strains Confer Resistance to Murine Norovirus Infection in a Cell Type-Dependent Manner. Journal of virology 3 32581099
2017 Astrocytic Expression of the Immunoreceptor CD300f Protects Hippocampal Neurons from Amyloid-β Oligomer Toxicity In Vitro. Current Alzheimer research 3 28155597
2025 Inhibitory immunoreceptors CD300a and CD300lf cooperate to regulate mast cell activation. Journal of immunology (Baltimore, Md. : 1950) 2 40073110
2025 Quercetin Alleviates Chronic Urticaria by Negatively Regulating IgE-Mediated Mast Cell Activation Through CD300f. Phytotherapy research : PTR 2 40309955
2025 CD300f enables microglial damage sensing, efferocytosis, and apoptotic cell metabolization after brain injury. Brain, behavior, and immunity 2 40935207
2025 Phosphatidylserine-binding receptor, CD300f, on macrophages mediates host invasion of pathogenic and non-pathogenic rickettsiae. bioRxiv : the preprint server for biology 1 38766217
2025 Phosphatidylserine-binding receptor, CD300f, on macrophages mediates host invasion of pathogenic and non-pathogenic rickettsiae. Infection and immunity 0 40310290
2025 Transcriptome profiling reveals abnormal cell wall components in the cleistogamy mutant 1 (clm1) lodicule of foxtail millet. Planta 0 40394337
2024 [Protective effect and mechanism of Zuogui Jiangtang Jieyu Formula on damage to hippocampal synaptic microenvironment in rats with diabetes-related depression based on microglia-neuron crosstalk signal CD300f/TLR4]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 0 39307798