Affinage

CD300LF

CMRF35-like molecule 1 · UniProt Q8TDQ1

Length
290 aa
Mass
32.3 kDa
Annotated
2026-06-09
59 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD300LF (IREM-1/CLM-1/MAIR-V/LMIR3/CD300f) is a myeloid immunoreceptor that senses lipids displayed on apoptotic cells and activated membranes and converts that recognition into bidirectional control of phagocytosis and inflammatory signaling (PMID:21865548, PMID:24477292, PMID:21536801). Its extracellular Ig-V-like domain binds phosphatidylserine in a metal ion-dependent manner inhibitable by Annexin V, and also binds ceramide, enabling recognition of apoptotic cells, microbes, and activated cell surfaces (PMID:21865548, PMID:25673319, PMID:40073110). Ligand engagement is read out through the cytoplasmic tail: phosphorylated ITIM tyrosines Y205 and Y249 dock SHP-1 (and, distinctively from CD300a, also SHP-2) to suppress FcεRI degranulation and both MyD88- and TRIF-dependent TLR/NF-κB signaling, while Y276 recruits the PI3K p85α subunit to activate Rac/Cdc42-driven F-actin remodeling at phagocytic cups and promote efferocytosis (PMID:15549731, PMID:17202342, PMID:22043923, PMID:24477292). This dual output makes the receptor a positive driver of apoptotic-cell engulfment in macrophages but an inhibitor in dendritic cells, where its loss causes hyperactive efferocytosis, excess TNF-α, and downstream T-cell-driven autoimmunity and colitis (PMID:24477292, PMID:26768664, PMID:28414292). Across mast cells, eosinophils, and neutrophils, ceramide- or PS-CD300LF engagement restrains mediator release and chemotaxis, dampening allergic, anaphylactic, septic, and inflammatory bone-loss responses (PMID:23820751, PMID:25673319, PMID:28073916, PMID:28655892, PMID:40073110, PMID:36089906). Independently of its inhibitory signaling, the CD300LF ectodomain is the physiologic entry receptor for murine norovirus, engaging the viral capsid P domain at a metal-dependent, bile-acid-modulated interface that mimics host phosphocholine binding, with cell-type-specific tropism determined by CC' loop residues (PMID:27681626, PMID:30194229, PMID:32251490, PMID:32581099, PMID:33177207). CD300LF also serves as an engulfment receptor for Rickettsia via rickettsial phosphatidylserine and, in the brain, as a microglial damage-sensing receptor coupling purinergic UDP-P2RY6 signaling and STING-pathway inhibition to neuroprotection (PMID:40310290, PMID:40935207, PMID:38965803).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2004 High

    Establishing CD300LF as an inhibitory receptor required showing it recruits a phosphatase and dampens activation, which defined its core signaling logic.

    Evidence Three-hybrid screen, reciprocal co-IP, and FcεR cross-linking assays in myeloid/U937 cells identifying SHP-1 recruitment via Y205

    PMID:15549731

    Open questions at the time
    • Physiologic ligand triggering phosphorylation unknown
    • Second ITIM contribution not yet mapped
  2. 2007 High

    Dissecting the cytoplasmic tail showed the receptor encodes both inhibitory and latent activating outputs, explaining how a single tail can branch signaling.

    Evidence Site-directed mutagenesis of cytoplasmic tyrosines plus beta-hexosaminidase secretion assays and PI3K inhibitors in RBL cells

    PMID:17202342

    Open questions at the time
    • Physiologic conditions favoring activating versus inhibitory output not defined
  3. 2007 High

    Solving the ectodomain structure revealed an Ig-V fold with a candidate ligand-discrimination loop, framing how CD300LF might engage ligands.

    Evidence X-ray crystallography of the IREM-1 Ig-V-like domain at 2.6 Å

    PMID:17275839

    Open questions at the time
    • No ligand bound in structure
    • Functional validation of the proposed binding groove absent
  4. 2008 Medium

    Cross-linking induced an ITIM-independent caspase-independent cell death, indicating the cytoplasmic region carries signaling functions beyond classic inhibition.

    Evidence Anti-CD300LF cross-linking with domain-deletion constructs and pharmacological inhibitors in peritoneal macrophages

    PMID:18097021

    Open questions at the time
    • Death effector pathway unidentified
    • Physiologic relevance of cross-linking-induced death unclear
  5. 2009 Medium

    An in vivo knockout established CD300LF as a negative regulator of myeloid effector function in neuroinflammation, linking its signaling to disease outcome.

    Evidence CLM-1 knockout mice in EAE with histology, cytokine and flow-cytometric readouts

    PMID:20038601

    Open questions at the time
    • Ligand and proximal signaling in vivo not defined
    • Microglial versus peripheral myeloid contribution unresolved
  6. 2011 High

    Identifying phosphatidylserine as a metal-dependent ligand connected receptor recognition to apoptotic cell clearance, defining its physiologic agonist.

    Evidence CD300f/Fc binding by ELISA, cosedimentation, SPR with liposomes, Annexin V competition, and ectopic-expression phagocytosis assays

    PMID:21865548

    Open questions at the time
    • Structural basis of metal-dependent PS binding not shown
    • Endogenous receptor engagement kinetics unknown
  7. 2011 High

    Mapping CD300LF's suppression of both MyD88 and TRIF arms of TLR signaling placed it as a broad innate-immune brake via SHP-1/NF-κB.

    Evidence mAb cross-linking and ITIM peptides with luciferase reporters, Western blot, and IP across TLR2/3/4/9 in monocytic cells

    PMID:21536801 PMID:22043923

    Open questions at the time
    • Relative SHP-1 versus SHP-2 contribution to TRIF inhibition only partly resolved
  8. 2013 High

    Showing CD300LF specifically restrains eotaxin/CCR3-driven eosinophil chemotaxis demonstrated pathway-selective inhibitory control over cell migration.

    Evidence Clm1-/- eosinophils in chemotaxis, calcium flux, ERK assays plus PS ligand addition and an allergic airway model

    PMID:23820751

    Open questions at the time
    • Molecular link between receptor and ERK/actin machinery in eosinophils not mapped
  9. 2014 High

    Defining the Y276-PI3K-Rac/Cdc42-F-actin axis at the phagocytic cup explained how the same receptor positively drives efferocytosis in macrophages.

    Evidence Cytoplasmic tyrosine mutagenesis, confocal imaging, p85α co-IP, GTPase/F-actin assays, KO macrophage phagocytosis, and a lupus-like model

    PMID:24477292

    Open questions at the time
    • Switch governing positive versus negative tyrosine motifs in vivo unclear
  10. 2015 High

    Identifying ceramide as a second ligand and its physical association with IL-4Rα broadened the receptor's ligand repertoire and signaling partnerships.

    Evidence CD300f-/- and mast-cell-specific reconstitution with ceramide functional assays and liposome rescue in colitis; co-localization with IL-4Rα in allergen challenge

    PMID:25673319 PMID:26124135

    Open questions at the time
    • Structural basis of ceramide binding not determined
    • Mechanism of IL-4Rα amplification not defined
  11. 2016 High

    Discovering CD300LF as the murine norovirus entry receptor revealed a ligand-independent function of the ectodomain as a viral receptor dictating tropism.

    Evidence Genome-wide CRISPR screen, antibody blocking, and ectopic expression conferring permissivity in heterologous cells

    PMID:27681626

    Open questions at the time
    • Structural details of capsid engagement not yet shown at this stage
    • Role in vivo not yet established
  12. 2016 Medium

    Demonstrating opposite efferocytic roles in dendritic cells versus macrophages established cell-type context as a determinant of CD300LF function and autoimmunity risk.

    Evidence Cd300f-/- DC efferocytosis, antigen-processing, T-cell priming, and ANA assays

    PMID:26768664

    Open questions at the time
    • Molecular basis of the macrophage/DC inversion unresolved
  13. 2017 High

    Multiple in vivo models established ceramide-CD300LF as a negative-feedback brake on mast cell/neutrophil mediator release across skin inflammation, sepsis, and gut inflammation.

    Evidence CD300f-/- mice with adoptive transfer and ceramide vesicle/antibody manipulation in skin pouch, CLP, and DSS colitis models

    PMID:28073916 PMID:28414292 PMID:28655892

    Open questions at the time
    • Source and regulation of extracellular ceramide in vivo incompletely defined
  14. 2018 High

    Co-crystal structures of CD300LF with the norovirus P domain defined the receptor-capsid interface and showed viral engagement mimics host phosphocholine binding with shared metal coordination.

    Evidence Multiple X-ray structures (P domain, phosphocholine, bile acid complexes) with SPR/ITC and interface mutagenesis

    PMID:29563286 PMID:30194229

    Open questions at the time
    • How bile acids allosterically enhance low monomeric affinity not fully resolved
  15. 2018 Medium

    A neutrophil KO phenotype showed CD300LF restrains antimicrobial effector activity and is itself induced by infection through TLR4/MyD88, adding a feedback loop to innate defense.

    Evidence LMIR3-KO neutrophil HOCl/elastase/cytotoxicity assays against P. aeruginosa and C. albicans with TLR4/MyD88 dependency

    PMID:30479367

    Open questions at the time
    • Ligand engaging CD300LF on infected neutrophils not identified
  16. 2020 High

    Genetic and conditional models established CD300LF as the sole physiologic norovirus receptor in vivo with cell-type- and strain-specific tropism, and excluded human norovirus use.

    Evidence CD300lf-/- and conditional Cre-driver mice, oral/parenteral MNoV infection, STAT1 crosses, and huCD300lf HNoV VLP binding tests; inbred strain CC' loop domain swaps

    PMID:32251490 PMID:32581099 PMID:33177207

    Open questions at the time
    • Determinants of tuft-cell versus myelomonocytic targeting incompletely defined
  17. 2020 Medium

    A functional cytoplasmic-tail SNP and KO neurobehavioral phenotype linked CD300LF to microglial metabolic fitness and depression-related behavior, extending its role into the brain.

    Evidence Human SNP association (rs2034310), Cd300f-/- behavioral phenotyping, RNA-seq, and biochemical metabolic studies

    PMID:32152116

    Open questions at the time
    • Causal pathway from PKC-site phosphorylation to behavior not established
  18. 2022 Medium

    Showing ceramide-CD300LF suppresses osteoclastogenesis extended the receptor's inhibitory ligand axis to bone homeostasis.

    Evidence CD300lf-/- mice in ligature-induced periodontitis with ceramide application in vitro and in vivo

    PMID:36089906

    Open questions at the time
    • Signaling downstream of CD300LF in osteoclast precursors not defined
  19. 2023 Medium

    Human monocyte/macrophage studies tied CD300LF signaling to PD-L1 upregulation, M2 polarization, and T-cell suppression via PI3K/Akt, framing an immunoregulatory output in humans.

    Evidence Anti-CD300f mAb cross-linking with T-cell proliferation, M1/M2 markers, and PI3K/Akt inhibition

    PMID:37302321

    Open questions at the time
    • Physiologic ligand driving human monocyte CD274 induction unidentified
  20. 2024 High

    Intravital imaging and proteomics established CD300LF as a microglial damage sensor coupling purinergic UDP-P2RY6 signaling and STING inhibition to apoptotic-debris clearance and neuroprotection.

    Evidence CD300LF-/- mice in mTBI/CCI models with two-photon imaging, proteomics, ENTPD6/P2RY6 quantification, and STING inhibitor C-176

    PMID:38965803 PMID:40935207

    Open questions at the time
    • Direct biochemical link between CD300LF and STING or P2RY6 not established
    • Whether ligand binding initiates damage sensing in brain unknown
  21. 2025 High

    Demonstrating CD300LF-mediated engulfment of Rickettsia via bacterial phosphatidylserine and cooperative mast-cell inhibition with CD300a refined its dual roles in host defense and allergy.

    Evidence CD300f-/- BMDM engulfment/infection assays with adoptive transfer; Cd300a-/-Cd300lf-/- double-KO imaging and anaphylaxis model

    PMID:40073110 PMID:40310290

    Open questions at the time
    • Mechanism of CD300a/CD300lf functional cooperation at the membrane not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD300LF integrates its multiple ligands (PS, ceramide) and divergent outputs (efferocytosis, inhibition, viral entry, damage sensing) into context-specific decisions across cell types remains unresolved.
  • No unified model linking ligand identity to inhibitory versus phagocytic output
  • Direct biochemical coupling to STING and P2RY6 axes unproven
  • Human in vivo functions largely uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0001618 virus receptor activity 4 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4 GO:0038024 cargo receptor activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3
Partners
CD300AIL4RAP2RY6PIK3R1PTPN11PTPN6

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 CD300LF (IREM-1) was identified as a novel inhibitory receptor that interacts with the SH2 domains of SHP-1 via a three-hybrid strategy. Western blot confirmed SHP-1 recruitment to IREM-1, with phosphotyrosine Y205 identified as the main docking site. Cross-linking of IREM-1 inhibits FcεR-induced activation in myeloid cells. The receptor contains two ITIM motifs and is expressed on monocytes and granulocytes. Three-hybrid screen, Western blot, immunoprecipitation, FACS, cross-linking functional assay European journal of immunology High 15549731
2007 CD300LF (IREM-1) cytoplasmic domain recruits both SHP-1 and the p85α subunit of PI3K. Y205 and Y249 (ITIM residues) are critical for IREM-1-mediated inhibition of FcεRI-induced degranulation. Mutation of Y205, Y249, Y284 (which abolishes SHP-1 binding) creates an activating receptor that promotes degranulation via PI3K through Y236 and Y263; this activation is blocked by wortmannin and LY-294002. Immunoprecipitation, site-directed mutagenesis of IREM-1 cytoplasmic tyrosines, functional beta-hexosaminidase secretion assay in RBL cells, PI3K inhibitor studies Journal of immunology High 17202342
2007 Crystal structure of the extracellular Ig-V-like domain of IREM-1 (CD300LF) was determined at 2.6 Å resolution. The fold resembles a V-type immunoglobulin domain with close homology to CLM-1, TREM-1, TLT-1, and NKp44. Structural analysis identified a hydrophobic groove on the surface and a structurally variable CDR3-equivalent loop proposed as the main determinant for ligand discrimination. X-ray crystallography at 2.6 Å resolution Journal of molecular biology High 17275839
2008 Cross-linking of CD300LF (MAIR-V) with anti-CD300LF mAb induces caspase-independent, ER stress-independent cell death in peritoneal macrophages and transfectants. This cell death requires the cytoplasmic region but not ITIM or ITSM motifs. Morphologically the dead cells resemble apoptotic cells (loss of blebs) but are resistant to caspase inhibitor Z-VAD-FMK and autophagy inhibitors. Anti-CD300LF cross-linking, scanning electron microscopy, pharmacological inhibition (Z-VAD-FMK, 3-methyladenine, N-acetyl-L-cysteine), Western blot for XBP-1 splicing, cytoplasmic domain deletion constructs Journal of immunology Medium 18097021
2009 CLM-1 (CD300LF) acts as a negative regulator of myeloid cells in autoimmune demyelination (EAE model). CLM-1-deficient mice showed increased nitric oxide and proinflammatory cytokine production by myeloid cells in demyelinating spinal cord, increased demyelination, and worse clinical scores, without affecting T cell responses in the periphery or spinal cord. CLM-1 knockout mouse model, EAE induction, histological scoring, cytokine measurement, flow cytometry of T cells The Journal of experimental medicine Medium 20038601
2011 CD300f (mouse) binds phosphatidylserine (PS) exposed on the outer membrane of apoptotic cells; this binding requires a metal ion. CD300f/Fc chimeric protein specifically binds apoptotic cells in a manner inhibitable by Annexin V. Binding was demonstrated by ELISA, cosedimentation, and surface plasmon resonance using phospholipid-containing liposomes. Ectopic expression of CD300f in cell lines enhances phagocytosis of apoptotic cells. CD300f/Fc chimeric protein binding assays, ELISA, cosedimentation, surface plasmon resonance with liposomes, Annexin V competition, ectopic expression phagocytosis assay Journal of immunology High 21865548
2011 CD300F blocks both MyD88 and TRIF-mediated TLR signaling in monocytic cells through recruitment of SHP-1. CD300F stimulation (mAb cross-linking or ITIM synthetic peptides) suppressed TLR2, 3, 4, and 9-mediated expression of IL-8 and MMP-9, inhibited IKK activation, IκB phosphorylation/degradation, and NF-κB activation. Immunoprecipitation confirmed SHP-1 association. mAb cross-linking, synthetic ITIM peptides, luciferase reporter assays, Western blot, immunoprecipitation, pharmacological inhibitors Journal of immunology High 21536801
2012 CD300f blocks both MyD88 and TRIF-mediated TLR signaling through combined activation of SHP-1 and SHP-2, whereas CD300a only blocks MyD88-mediated signaling via SHP-1. Differential inhibition is recapitulated by synthetic ITIM peptides of CD300a versus CD300f. This distinction maps to the ability of CD300f (but not CD300a) to activate SHP-2 for TRIF pathway inhibition. TLR stimulation in THP-1/U937 cells, NF-κB luciferase reporter, synthetic ITIM peptides, signaling inhibitors, Western blot Immunology Medium 22043923
2013 CLM-1 (CD300f) negatively regulates eotaxin-induced eosinophil chemotaxis, actin polymerization, calcium influx, and ERK1/2 (but not p38) phosphorylation. Addition of CLM-1 ligand phosphatidylserine rendered wild-type eosinophils hypochemotactic in vitro; blockade of CLM-1/ligand interactions caused hyperchemotaxis in vitro and in an allergic airway model in vivo. CLM-1 regulation was specific to eotaxin/CCR3 and not LTB4 or MIP-1α. Clm1-/- mouse eosinophils, in vitro chemotaxis assay, calcium flux, ERK/p38 phosphorylation, in vivo allergic airway model, phosphatidylserine ligand addition Mucosal immunology High 23820751
2014 CD300f (CLM-1) accumulates in phagocytic cups at apoptotic cell contact sites. Phosphorylation of Y276 in the cytoplasmic tail recruits the p85α subunit of PI3K, which activates downstream Rac/Cdc42 GTPase and drives F-actin remodeling to promote apoptotic cell engulfment. Y276 phosphorylation is required for enhanced phagocytosis. Distinct tyrosine motifs positively (Y276/PI3K) or negatively regulate phagocytosis. Primary CD300f-deficient macrophages show impaired apoptotic cell phagocytosis. CD300f deficiency in FcγRIIB-null mice accelerates lupus-like disease. Site-directed mutagenesis of CD300f cytoplasmic tyrosines, confocal microscopy, PI3K co-immunoprecipitation, Rac/Cdc42 activation assays, F-actin imaging, CD300f-/- macrophage phagocytosis, autoimmune disease model Nature communications High 24477292
2015 CD300f binds ceramide as a ligand and this interaction suppresses IgE-dependent and mast cell-dependent allergic responses. In the DSS colitis model, ceramide-CD300f (LMIR3) binding inhibited ATP-stimulated mast cell activation. CD300f deficiency exacerbated DSS-induced colitis; mast cell-specific CD300f deficiency was responsible. Administration of ceramide liposomes suppressed colitis; disruption of ceramide-LMIR3 interaction aggravated it. CD300f-/- mice, mast cell-deficient Kit(W-sh) mice, BMMC reconstitution, ATP-stimulated BMMC in vitro activation, ELISA, ceramide liposome treatment, DSS colitis model Gut High 25673319
2015 CD300f is colocalized and physically associated with IL-4Rα in macrophages. CD300f amplifies IL-4Rα-induced signaling, mediator release, and priming. Cd300f-/- cells and mice show decreased IL-4/IL-13-induced responses, IgE production, chemokine expression, and inflammatory cell recruitment in allergen challenge, while IL-4/IL-13 levels are increased (consistent with decreased cytokine consumption). Co-localization microscopy, physical association assay, Cd300f-/- cells and mice, IL-4Rα cross-linking, allergen challenge model, cytokine ELISA Proceedings of the National Academy of Sciences of the United States of America High 26124135
2016 CD300lf and CD300ld are functional cell-surface receptors for murine norovirus (MNV). Identified by genome-wide CRISPR/Cas9 screen. Anti-CD300lf polyclonal antibody significantly reduces viral progeny. Ectopic expression of CD300lf in non-susceptible cell lines from other species enables MNV infection and progeny production, demonstrating CD300lf is sufficient to confer permissivity and can dictate host tropism. Genome-wide CRISPR/Cas9 loss-of-function screen, antibody blocking, ectopic expression in heterologous cell lines, viral progeny quantification Proceedings of the National Academy of Sciences of the United States of America High 27681626
2016 CD300f expression in dendritic cells (DCs) inhibits efferocytosis (in contrast to its function in macrophages where it promotes phagocytosis). CD300f deficiency in DCs leads to hyperactive phagocytosis of apoptotic cells, enhanced antigen processing and T-cell priming, expansion of memory T cells, and increased ANA levels. This contributes to autoimmune disease predisposition. Cd300f-/- mouse DCs, efferocytosis assays, antigen presentation assays, T cell priming, ANA measurement, apoptotic cell overload model Cell death and differentiation Medium 26768664
2017 Ceramide-CD300f binding inhibits LPS-induced skin inflammation. CD300f deficiency enhanced LPS-induced skin edema and neutrophil recruitment. CD300f suppresses release of chemical mediators (vascular permeability factors, neutrophil chemoattractants) from mast cells and neutrophils in response to LPS. Adoptive transfer experiments demonstrated mast cell and neutrophil contributions. Ceramide antibody enhanced and ceramide-containing vesicles suppressed LPS-induced skin inflammation. CD300f-/- mice, skin pouch model, LPS injection, adoptive mast cell transfer, ceramide antibody/vesicle administration, flow cytometry, mediator ELISA The Journal of biological chemistry High 28073916
2017 CD300f-expressing DCs play a crucial role in resolving gut inflammation. CD300f-deficient DCs show hyperactive phagocytosis of apoptotic cells, stimulating excessive TNF-α secretion predominantly from DCs, which induces secondary IFN-γ overproduction by colonic T cells, leading to prolonged gut inflammation. Abnormal apoptotic cell accumulation in the gut of CD300f-deficient mice was observed. CD300f-/- mouse colitis model (DSS), DC-specific functional assays, apoptotic cell accumulation imaging, cytokine measurement (TNF-α, IFN-γ), T cell analysis The Journal of clinical investigation High 28414292
2017 Ceramide-CD300f interaction suppresses neutrophil chemoattractant production from mast cells and neutrophils in the context of septic peritonitis (CLP model). CD300f-/- mice are protected from CLP-induced death; CD300f deficiency enhances neutrophil accumulation and bacterial clearance. Extracellular ceramide concentrations increase in the peritoneal cavity after CLP, suggesting a negative-feedback role for ceramide-CD300f in innate immunity. CD300f-/- mice, CLP model, mast cell-deficient mouse reconstitution with WT/CD300f-/- mast cells and neutrophils, in vitro E. coli stimulation of MCs/neutrophils, ceramide vesicle/antibody administration, bacterial burden quantification Scientific reports High 28655892
2018 X-ray crystal structure of the MNoV VP1 protruding (P) domain in complex with CD300lf was determined. CD300lf binds the P domain with 2:2 stoichiometry at a cleft between AB and DE loops of the P2 subdomain overlapping neutralizing antibody epitopes. Two bile acid binding sites were identified at the P domain dimer interface distant from receptor binding sites. CD300lf engages MNoV in a manner mimicking host ligand (phosphocholine) binding including similar metal coordination. Monomeric affinity of CD300lf for P domain is low and divalent cation dependent. X-ray crystallography (CD300lf–P domain complex, CD300lf–phosphocholine complex, CD300lf–bile acid complexes), biophysical assays (SPR, ITC), interface residue mutagenesis, cryo-EM docking Proceedings of the National Academy of Sciences of the United States of America High 30194229
2018 Crystal structure of soluble CD300lf in complex with the MNoV capsid protruding domain was determined at 2.05 Å resolution. The CD300lf binding site is on the topside of the P domain, involving hydrophilic and hydrophobic interactions, with CD300lf fitting into a complementary cavity stabilized by complementary surface charges. Five of six P domain residues interacting with CD300lf are conserved across MNoV strains. CD300lf-interacting residues are partially conserved in CD300ld but variable in other CD300 family members, consistent with observed infection selectivity. X-ray crystallography at 2.05 Å resolution, sequence alignment analysis Journal of virology High 29563286
2018 LMIR3/CD300f deficiency augments antimicrobial activity of mouse neutrophils. LMIR3-KO neutrophils show significantly increased hypochlorous acid production, elastase release, and cytotoxic activity against P. aeruginosa and C. albicans. LMIR3 surface expression increases on bone marrow neutrophils in response to P. aeruginosa infection in a TLR4/MyD88-dependent manner. Elastase and myeloperoxidase inhibitors offset the enhanced antimicrobial activity of KO neutrophils. LMIR3-KO mice, hypochlorous acid production assay, elastase release assay, cytotoxicity assay, P. aeruginosa/C. albicans infection models, TLR4/MyD88 dependency via inhibitors Scientific reports Medium 30479367
2020 CD300lf is the sole physiologic receptor for MNoV in vivo. CD300lf is required for both oral and parenteral MNoV infection and for anti-MNoV humoral responses. In STAT1-deficient mice, CD300lf is required for MNoV-induced lethality. Human CD300lf (huCD300lf) is not an entry receptor for human norovirus (HNoV) and does not inhibit HNoV virus-like particle binding to glycans. CD300lf-/- mice, oral and parenteral MNoV infection, anti-MNoV antibody ELISA, STAT1-/- x CD300lf-/- double KO lethality model, HNoV VLP binding assay with huCD300lf PLoS pathogens High 32251490
2020 A non-synonymous SNP (rs2034310, C/T) in the CD300f cytoplasmic tail inhibits protein kinase C phosphorylation of a threonine residue and is associated with protection against major depressive disorder, mainly in women. CD300f-/- mice display augmented microglial numbers, increased IL-6 and IL-1Ra mRNA, synaptic strength alterations, and noradrenaline-dependent depressive-like behaviors in females. RNA sequencing and biochemical studies indicate impaired microglial metabolic fitness in CD300f-/- mice. Human genetic association (SNP analysis), CD300f-/- mouse behavioral phenotyping, RNA sequencing, biochemical metabolic studies, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America Medium 32152116
2020 CD300LF polymorphisms in inbred mouse strains (I/LnJ vs C57BL/6J) confer resistance to MNV infection in a cell type-dependent manner. A 4-amino-acid difference in the CC' loop of CD300LF determines functional receptor activity. I/LnJ CD300LF does not function as MNV entry factor in macrophage-like cells but does in other cell types. I/LnJ CD300LF binds MNV virions in permissive but not non-permissive cells, indicating a cell type-specific modifier of CD300LF-dependent MNV entry. Bone marrow-derived macrophage infection assays, lentiviral transduction with C57BL/6J vs I/LnJ CD300LF swap constructs, chimeric receptor mutagenesis, virion binding assay Journal of virology High 32581099
2021 CD300lf expression on intestinal epithelial tuft cells is essential for transmission of persistent MNoV strain CR6, demonstrated using a conditional CD300lf knockout mouse. The non-persistent MNoV strain CW3 does not require CD300lf on IECs but utilizes myelomonocytic cells (LysM+ cells) as a major target. CD300lf on B cells, neutrophils, and dendritic cells is not critical for CW3 infection. STAT1 signaling partially restricts CW3 tropism to LysM+ cells. Conditional Cd300lf knockout mice (IEC-specific, LysM-Cre, CD19-Cre, Mrp8-Cre, CD11c-Cre), MNoV infection, viral RNA quantification, STAT1-/- genetic crosses Journal of virology High 33177207
2022 CD300lf-ceramide interaction inhibits osteoclast differentiation. CD300lf expression is downregulated during osteoclastogenesis. CD300lf ablation increases osteoclast numbers and exacerbates alveolar bone loss in a ligature-induced periodontitis model. Application of ceramide (CD300lf ligand) suppresses osteoclastogenesis in vitro and inhibits alveolar bone loss in vivo. CD300lf-/- mice, ligature-induced periodontitis model, osteoclast counting, ceramide application in vitro and in vivo, bone resorption quantification Journal of clinical periodontology Medium 36089906
2023 CD300f signaling in human monocytes via anti-CD300f mAb cross-linking (DCR-2) suppresses monocytes by upregulating CD274 (PD-L1) and inhibiting T cell proliferation. In macrophages, CD300f signaling drives M2-type polarization with CD274 upregulation further enhanced by IL-4. CD300f signaling activates the PI3K/Akt pathway in monocytes; PI3K/Akt inhibition reduces CD274 expression. Anti-CD300f mAb cross-linking, T cell proliferation assay, M1/M2 polarization marker flow cytometry, PI3K/Akt pharmacological inhibition, Western blot Cellular immunology Medium 37302321
2024 CD300LF-deficient microglia fail to extend processes toward laser-induced cortical lesions (intravital two-photon microscopy), indicating CD300LF is required for microglial detection of damage-associated cues. CD300LF-/- microglia show reduced recognition and clearance of apoptotic cells after mTBI and intracortical apoptotic cell injection, with apoptotic cell remnants retained intracellularly suggesting defective phagolysosomal processing. Proteomic analysis after CCI reveals dysregulation of autophagy-related and metabolic pathways. CD300LF deficiency alters the UDP-P2RY6 axis with upregulation of ENTPD6 and downregulation of P2ry6, implicating impaired purinergic damage sensing. Intravital two-photon microscopy, CD300LF-/- mice, mTBI and CCI models, intracortical apoptotic cell injection, flow cytometry, proteomics, ENTPD6/P2RY6 mRNA/protein quantification Brain, behavior, and immunity High 40935207
2024 CD300LF-deficient mice show increased glial proliferation, neuronal loss, and worse neurological function after TBI. Transcriptomic comparison of CD300LF+ vs CD300LF- microglia reveals that CD300LF's neuroprotective role is principally mediated by inhibition of the STING signaling pathway. The STING pathway inhibitor C-176 augments the protective effect. CD300LF-/- mice, TBI model, transcriptomics (RNA-seq of sorted microglia populations), STING inhibitor C-176 treatment, histological and neurological function scoring CNS neuroscience & therapeutics Medium 38965803
2025 CD300f mediates engulfment of pathogenic Rickettsia species (R. typhi, R. rickettsii) and non-pathogenic R. montanensis by macrophages, using rickettsial phosphatidylserine (PS) as the ligand. CD300f-/- BMDMs show significantly reduced rickettsial engulfment. CD300f-/- mice are protected from fatal rickettsiosis (R. typhi, R. rickettsii) with reduced bacterial burden. Adoptive transfer of CD300f-expressing macrophages restores susceptibility to rickettsiosis in vivo. CD300f-/- bone marrow-derived macrophages, infection assays with multiple Rickettsia species, in vivo infection model, bacterial burden quantification (spleen), adoptive macrophage transfer Infection and immunity High 40310290
2025 CD300lf and CD300a colocalize with phosphatidylserine externalized to the outer leaflet of the plasma membrane in a polar formation upon mast cell activation, and cooperate to inhibit mast cell activation. CD300lf also colocalizes with extracellular ceramide on the cell surface, and CD300lf binding to ceramide produces stronger inhibition of mast cell activation than binding to PS alone. Double-KO (Cd300a-/-Cd300lf-/-) mice show exacerbated passive systemic anaphylaxis compared to single KOs. Imaging and flow cytometry of BMMCs from WT, Cd300a-/-, Cd300lf-/-, Cd300a-/-Cd300lf-/- mice, PS/ceramide colocalization, passive systemic anaphylaxis model Journal of immunology High 40073110

Source papers

Stage 0 corpus · 59 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 147 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 93 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) 83 21865548
2014 p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression. Nature communications 80 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 65 32251490
2009 CLM1 of Fusarium graminearum encodes a longiborneol synthase required for culmorin production. Applied and environmental microbiology 62 19880637
2015 Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation. Gut 56 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 56 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 55 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 46 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) 44 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 37 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 36 26768664
2018 Atomic Structure of the Murine Norovirus Protruding Domain and Soluble CD300lf Receptor Complex. Journal of virology 33 29563286
2013 CMRF35-like molecule 1 (CLM-1) regulates eosinophil homeostasis by suppressing cellular chemotaxis. Mucosal immunology 32 23820751
2017 Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment. Scientific reports 30 28655892
2011 Overexpression of the immunoreceptor CD300f has a neuroprotective role in a model of acute brain injury. Brain pathology (Zurich, Switzerland) 30 21951326
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
2007 The crystal structure of the extracellular domain of the inhibitor receptor expressed on myeloid cells IREM-1. Journal of molecular biology 29 17275839
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
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 24 28725048
2009 Monoclonal antibodies against IREM-1: potential for targeted therapy of AML. Leukemia 21 19440216
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 18 31501529
2024 CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway. CNS neuroscience & therapeutics 14 38965803
2023 CD300f immune receptor contributes to healthy aging by regulating inflammaging, metabolism, and cognitive decline. Cell reports 13 37864797
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
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 13 22288587
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
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
2022 Clarithromycin-treated chronic spontaneous urticaria with the negative regulation of FcεRΙ and MRGPRX2 activation via CD300f. International immunopharmacology 10 35853276
2018 Mouse LIMR3/CD300f is a negative regulator of the antimicrobial activity of neutrophils. Scientific reports 10 30479367
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
2024 Intranasal administration of ceramide liposome suppresses allergic rhinitis by targeting CD300f in murine models. Scientific reports 5 38600251
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
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

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