Affinage

LAIR1

Leukocyte-associated immunoglobulin-like receptor 1 · UniProt Q6GTX8

Length
287 aa
Mass
31.5 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LAIR-1 (CD305) is a broadly expressed transmembrane immune inhibitory receptor with a single Ig-like domain and a cytoplasmic tail bearing two ITIMs that, upon cross-linking, recruits the phosphatases SHP-1 and SHP-2 to dampen activating signals — first established as a potent inhibitor of NK cell cytotoxicity (PMID:9285412). Its defining feature is recognition of extracellular matrix: collagens are high-affinity functional ligands whose binding depends on Gly-Pro-Hyp repeats and engages a binding surface (R59, E61, W109) structurally analogous to the platelet collagen receptor GPVI (PMID:16754721, PMID:20007810). Through this collagen sensing, LAIR-1 imposes inhibitory tone across diverse cell types — restraining BCR signaling in B cells, monocyte-to-DC differentiation, type I IFN production, ILC2 effector function via SHP1/PI3K/AKT, neutrophil recruitment, and osteoclastogenesis (PMID:10540327, PMID:23093673, PMID:34144112, PMID:31080449, PMID:30217615). Beyond collagen, LAIR-1 is engaged by additional collagen-domain or stromal ligands including C1q (via its collagen-like tail), Colec12, adiponectin globular domain, MARCO, and polymerized type I collagen, with the secreted homolog LAIR-2 acting as a high-affinity competitive antagonist (PMID:18209062, PMID:23093673, PMID:34260887, PMID:34403808, PMID:41364749, PMID:39940787). In the tissue setting LAIR-1 functions as a negative-feedback brake on tumor immunity and fibrosis: collagen-induced exhaustion of CD8+ T cells proceeds through LAIR1/SHP-1, and loss of functional collagen ligands in systemic sclerosis exacerbates fibrosis (PMID:32908154, PMID:38696927). In cancer cells LAIR-1 is co-opted for pro-tumorigenic signaling — in AML stem cells SHP-1 acts as a phosphatase-independent adaptor recruiting CAMK1 to activate CREB for survival and self-renewal, while in glioma it recruits SHP2 to drive FAK nuclear localization and oncogenic transcription (PMID:25915125, PMID:37845206). In megakaryocytes LAIR-1 restrains GPVI-FcRγ-driven Src family kinase activity in a pathway redundant with PECAM-1, limiting platelet reactivity (PMID:28336561, PMID:39318773). The malaria RIFIN antigens engage LAIR1 at a site overlapping the collagen-binding surface, and somatic insertion of the LAIR1 collagen-binding domain into antibody genes generates broadly reactive anti-RIFIN antibodies (PMID:26700814, PMID:34433057).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    Established LAIR-1 as an HLA-independent inhibitory receptor, answering whether its ITIMs functionally couple to phosphatases and suppress effector function.

    Evidence Antibody cross-linking on NK cells with phosphatase recruitment and cytotoxicity assays

    PMID:9285412

    Open questions at the time
    • Physiological ligand unknown at this point
    • Relative roles of SHP-1 vs SHP-2 not resolved
  2. 1999 Medium

    Extended LAIR-1 inhibitory function to B cell antigen receptor signaling and showed activation-dependent downregulation, defining its role across lymphocyte lineages.

    Evidence Co-cross-linking with BCR and intracellular calcium flux measurement plus expression profiling

    PMID:10540327

    Open questions at the time
    • Downstream effectors in B cells not delineated
    • Single lab
  3. 1998 Medium

    Showed LAIR-1 blocks myeloid differentiation by inhibiting GM-CSF receptor signaling, broadening its inhibitory scope to monocyte/DC development.

    Evidence Antibody cross-linking with monocyte-DC differentiation and calcium measurement

    PMID:9692876

    Open questions at the time
    • Mechanistic link to GM-CSFR signaling not molecularly defined
    • Single lab
  4. 2006 High

    Identified collagens as the first ECM ligands for an inhibitory immune receptor, answering the long-standing question of LAIR-1's physiological ligand.

    Evidence Cell-free and cell-surface binding assays with Gly-Pro-Hyp dependence and functional immune assays

    PMID:16754721

    Open questions at the time
    • Structural basis of recognition not yet defined
    • In vivo relevance of collagen engagement untested
  5. 2009 High

    Defined the structural basis of collagen recognition and revealed an unexpected shared mechanism with the platelet receptor GPVI.

    Evidence X-ray crystallography, NMR titrations, and site-directed mutagenesis identifying R59/E61/W109

    PMID:20007810

    Open questions at the time
    • Structure of receptor-ligand complex not solved
    • Conformational changes on engagement unknown
  6. 2008 High

    Identified the secreted homolog LAIR-2 as a higher-affinity competitive antagonist, establishing a natural mechanism for tuning LAIR-1 signaling.

    Evidence SPR, flow cytometry binding, adhesion, and cross-linking inhibition assays

    PMID:18209062

    Open questions at the time
    • In vivo regulatory role of LAIR-2 not established
  7. 2012 High

    Broadened the LAIR-1 ligand repertoire to C1q via its collagen-like tail, linking complement to inhibitory signaling in myeloid cells.

    Evidence Binding assays, ITIM phosphorylation, siRNA knockdown, and functional DC/IFN-α assays

    PMID:23093673

    Open questions at the time
    • Structural mode of C1q binding not yet defined here
  8. 2015 High

    Revealed a non-canonical, phosphatase-independent LAIR1-SHP-1-CAMK1-CREB axis sustaining AML stem cell survival, recasting an inhibitory receptor as a tumor dependency.

    Evidence shRNA knockdown, in vivo leukemia assays, Co-IP, and signaling pathway analysis

    PMID:25915125

    Open questions at the time
    • Ligand driving the AML pathway not defined
    • How SHP-1 switches from phosphatase to adaptor unclear
  9. 2017 High

    Demonstrated that LAIR-1 restrains GPVI-FcRγ Src kinase signaling in megakaryocytes to limit platelet hyperreactivity and thrombosis.

    Evidence LAIR-1 KO mouse with platelet counts, proplatelet formation, Src activity, and in vivo thrombosis model

    PMID:28336561

    Open questions at the time
    • Endogenous activating ligand in megakaryocytes not defined
  10. 2020 High

    Established collagen-LAIR1-SHP-1 as a driver of CD8+ T cell exhaustion and a checkpoint-resistance mechanism, linking matrix to anti-tumor immunity.

    Evidence Proteomic/RNA profiling, murine tumor models, LAIR2 overexpression, SHP-1 inhibition, LOXL2 knockdown

    PMID:32908154

    Open questions at the time
    • Relative contribution of T-cell-intrinsic vs stromal LAIR1 not fully separated
  11. 2021 High

    Defined the LAIR1 interactome including Colec12 and extended its myeloid role to monocyte/macrophage homeostasis, while structural studies mapped C1q and RIFIN engagement.

    Evidence Proteomic interactome, Lair1-/- mice, flow cytometry; crystallography of RIFIN-LAIR1 complexes and C1q CLR mutagenesis

    PMID:34066122 PMID:34144112 PMID:34244481 PMID:34260887 PMID:34403808 PMID:34433057

    Open questions at the time
    • Whether all newly identified ligands engage overlapping surfaces incompletely resolved
    • Adiponectin (gAdp) interaction rests on a single weaker study
  12. 2015 High

    Showed that the LAIR1 collagen-binding domain inserted into antibody genes confers broad anti-RIFIN reactivity, revealing pathogen exploitation and a novel antibody architecture.

    Evidence Monoclonal antibody isolation, antibody gene sequencing, domain mutagenesis, and erythrocyte/RIFIN binding; later Fab crystallography

    PMID:26700814 PMID:28527239

    Open questions at the time
    • Frequency and selection of such insertions in the population not addressed here
  13. 2023 Medium

    Showed LAIR1 drives glioma progression via SHP2-mediated FAK nuclear localization and oncogenic transcription, and that agonist antibodies selectively kill leukemic stem cells.

    Evidence Co-IP, ITIM mutagenesis, fractionation, glioma models; agonist antibody NC525 with xenograft models

    PMID:37845206 PMID:37966113

    Open questions at the time
    • Glioma mechanism from single lab
    • Generality of pro-tumor SHP2-FAK axis across tumor types untested
  14. 2024 High

    Established LAIR-1 as an essential negative-feedback brake on tissue repair and demonstrated functional redundancy with PECAM-1 in platelet signaling.

    Evidence LAIR-1 KO fibrosis models with MMP/PDGFR dissection; LAIR-1/PECAM-1 double KO epistasis with platelet aggregometry and Src signaling

    PMID:38696927 PMID:39318773

    Open questions at the time
    • How disorganized fibrotic collagen loses LAIR-1 ligand activity at structural level not resolved
  15. 2024 Medium

    Delineated multiple tumor-cell-intrinsic LAIR1 signaling axes (GSK-3β/β-catenin/MYC/PD-L1; AKT-IKKβ-p65; SHP-2/JAK2-STAT) coupling LAIR1 to immune evasion and proliferation control.

    Evidence Western blot, fractionation, co-culture with CD8+ T cells, Co-IP, and migration/proliferation assays in HCC and HEL cells

    PMID:38199599 PMID:38512030 PMID:39016636

    Open questions at the time
    • Each axis defined in a single lab/model
    • Reconciliation of inhibitory vs pro-tumor outcomes context-dependent
  16. 2025 High

    Identified MARCO as a bidirectional cis/trans regulator of LAIR-1 and confirmed polymerized collagen (PTIC) as a functional ligand, expanding the ligand and regulatory landscape.

    Evidence Single-molecule fluorescence microscopy, CRISPR-Cas9 KO, binding and signaling assays; SPR and pSTAT1 readouts for PTIC

    PMID:39940787 PMID:41364749

    Open questions at the time
    • In vivo relevance of cis MARCO-LAIR1 regulation not established
    • PTIC therapeutic studies single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LAIR-1 switches between classical SHP-1/SHP-2-dependent inhibition and the phosphatase-independent or pro-tumorigenic signaling modes — and what determines this choice across cell types and ligands — remains unresolved.
  • No unifying model linking ligand identity to SHP-1-adaptor vs phosphatase output
  • Structural basis of multi-ligand competition (collagen, C1q, MARCO, RIFIN) on one Ig domain incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-109582 Hemostasis 2 R-HSA-1474244 Extracellular matrix organization 2
Partners
C1QCAMK1COLEC12FAKMARCOPECAM-1SHP-1SHP-2

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 LAIR-1 is a 32 kDa transmembrane glycoprotein with a single immunoglobulin-like domain and a cytoplasmic tail containing two ITIMs. Cross-linking of LAIR-1 on NK cells recruits SHP-1 and SHP-2 phosphatases and results in strong inhibition of NK cell-mediated cytotoxicity. LAIR-1 does not recognize HLA class I molecules. Antibody cross-linking on NK cells, phosphatase recruitment assay, cytotoxicity assay Immunity High 9285412
2006 Collagens are high-affinity functional ligands for LAIR-1. The interaction depends on conserved Gly-Pro-Hyp collagen repeats. Collagen binding directly inhibits immune cell activation in vitro, establishing collagens as the first extracellular matrix ligands for an inhibitory immune receptor. Binding assays (cell-free and cell-surface), functional immune cell activation assays in vitro The Journal of experimental medicine High 16754721
2009 Crystal structure of LAIR-1 was determined and its collagen-binding site was mapped by NMR titrations and mutagenesis. Key residues R59, E61, and W109 are essential for collagen interaction. These residues are conserved between LAIR-1 and the platelet collagen receptor GPVI, revealing an unanticipated common structural mechanism of collagen recognition. X-ray crystallography, NMR titrations, site-directed mutagenesis Blood High 20007810
1999 LAIR-1 functions as a negative regulator of BCR-mediated signaling in B cells. Simultaneous cross-linking of LAIR-1 and the BCR reduces intracellular Ca2+ increase evoked by BCR ligation. LAIR-1 expression is lost during B cell activation (germinal center B cells, plasmablasts, plasma cells). Co-cross-linking assay, intracellular calcium flux measurement, flow cytometry for expression profiling European journal of immunology Medium 10540327
1998 LAIR-1 (p40) cross-linking prevents differentiation of CD14+ monocytes into dendritic cells induced by GM-CSF. Engagement of LAIR-1 inhibits GM-CSF receptor-mediated intracellular calcium increases in CD14+ and CD14+CD34+ cells, suggesting LAIR-1 blocks GM-CSF receptor signaling. Antibody cross-linking, morphological and phenotypic analysis, intracellular calcium measurement European journal of immunology Medium 9692876
2008 LAIR-2, a secreted homolog of LAIR-1, binds collagen with high affinity in a hydroxyproline-dependent manner and acts as a competitive antagonist of LAIR-1 by preventing collagen binding to LAIR-1 and blocking LAIR-1 cross-linking in vitro. Surface plasmon resonance, flow cytometry binding assays, adhesion assays, LAIR-1 cross-linking inhibition assay Journal of immunology High 18209062
2012 C1q is a functional ligand for LAIR-1. C1q and its collagen-like tail bind LAIR-1 and LAIR-2 in cell-free systems and on the cell membrane, trigger phosphorylation of LAIR-1 ITIMs in monocytes, and mediate inhibition of monocyte-DC differentiation and IFN-α production by plasmacytoid DCs. These effects were reversed by LAIR-2 and by LAIR-1 siRNA knockdown. Cell-free binding assays, cell surface binding assays, ITIM phosphorylation assay, siRNA knockdown, functional DC differentiation and IFN-α production assays Proceedings of the National Academy of Sciences of the United States of America High 23093673
2015 LAIR1 is essential for AML development. LAIR1 activates SHP-1, which acts as a phosphatase-independent signaling adaptor to recruit CAMK1, leading to activation of downstream CREB. This LAIR1-SHP-1-CAMK1-CREB pathway sustains survival and self-renewal of AML stem cells. Inhibition of LAIR1 expression abolishes leukemia development without affecting normal hematopoiesis. shRNA knockdown, in vivo leukemia development assays, co-immunoprecipitation, signaling pathway analysis Nature cell biology High 25915125
2011 Tumor-expressed transmembrane collagens bind LAIR-1 and activate LAIR-1 inhibitory signaling. LAIR-1-Fc fusion proteins and LAIR-1-expressing cells bind tumor cell-expressed collagens. Knockdown of prolyl 4-hydroxylase (required for collagen folding) diminishes LAIR-1 binding. Overexpression of collagen XVII on target cells diminishes NK cell cytotoxic activity. LAIR-1-Fc fusion protein binding assays, collagen knockdown by shRNA, NK cell cytotoxicity assay, flow cytometry Molecular immunology Medium 21955987
2015 C1q-mediated repression of monocytes is regulated through LAIR-1. C1q engagement of LAIR-1 enhances LAIR-1 ITIM phosphorylation and promotes interaction of LAIR-1 with SHP-1. C1q/LAIR-1 signaling inhibits nuclear translocation of IRF-3 and IRF-5 in CpG-stimulated monocytes, suppressing type I IFN production. LAIR-1 phosphorylation assay, Co-immunoprecipitation of LAIR-1 with SHP-1, nuclear translocation assay (IRF-3 and IRF-5) Molecular medicine Medium 25247291
2017 Mice lacking LAIR-1 exhibit increased platelet counts, prolonged platelet half-life, and increased proplatelet formation. LAIR-1 deficiency in megakaryocytes leads to enhanced Src family kinase activity and downstream signaling through the GPVI-FcRγ-chain and integrin αIIbβ3, which is transmitted to platelets making them hyperreactive to collagen/GPVI agonists. LAIR-1 inhibits GPVI-FcRγ signaling in megakaryocytes. LAIR-1 knockout mouse model, platelet count/half-life measurements, proplatelet formation assay, signaling analysis (Src kinase activity), thrombus formation (FeCl3 carotid artery model) Arteriosclerosis, thrombosis, and vascular biology High 28336561
2020 Collagen-induced T cell exhaustion occurs through LAIR1. CD18 interaction with collagen upregulates LAIR1 expression on CD8+ T cells, and LAIR1 induces T cell exhaustion through SHP-1. LAIR2 overexpression or SHP-1 inhibition sensitizes resistant tumors to anti-PD-1 therapy. LOXL2 suppression (reducing collagen deposition) increases T cell infiltration and reduces exhausted T cells. Proteomic and RNA profiling, murine tumor models, LAIR2 overexpression, SHP-1 inhibition, LOXL2 knockdown, flow cytometry for T cell phenotyping Nature communications High 32908154
2021 LAIR1 interacts with the stromal factor Colec12 as a high-affinity ligand (identified by proteomic definition of the LAIR1 interactome). LAIR1 signaling (triggered by Collagen1 and Colec12) activates pathways associated with survival, proliferation, and differentiation in myeloid cells. LAIR1 deficiency reduces Ly6C- non-classical monocyte frequencies due to altered proliferation and apoptosis, and alters interstitial macrophage heterogeneity in the lung. Proteomic interactome profiling, Lair1-/- mouse model, flow cytometry for monocyte/macrophage subsets, proliferation and apoptosis assays Immunity High 34260887
2018 Collagen type I degradation fragments inhibit osteoclast formation acting through LAIR-1. The inhibition requires LAIR-1, as collagen fragments failed to inhibit osteoclast formation from LAIR-1-deficient murine precursors. Collagen fragments signaled through SH-2 phosphatases, inhibiting calcium signaling and NFATc1 translocation in osteoclast precursors. LAIR-1 KO mouse osteoclast precursors, osteoclast differentiation assay, calcium signaling assay, NFATc1 nuclear translocation assay Bone High 30217615
2021 LAIR-1 is inducible on activated ILC2s and downregulates their cytokine secretion and effector function. LAIR-1 signaling in ILC2s is mediated via SHP1/PI3K/AKT inhibitory pathways. LAIR-1 deficiency leads to exacerbated ILC2-dependent airway hyperreactivity. Engagement of LAIR-1 by physiologic ligand C1q significantly reduced ILC2-dependent AHR in a humanized murine model. LAIR-1 knockout mice, adoptive transfer experiments, RNA sequencing, flow cytometry, antisense knockdown in human ILC2s, humanized mouse model The Journal of allergy and clinical immunology High 34144112
2019 LAIR-1 deficiency in mice enhances airway neutrophil recruitment and worsens inflammatory lung disease after RSV infection and cigarette smoke exposure. LAIR-1-Fc administration augments inflammation similarly. CXCL1-mediated neutrophil recruitment to airways is enhanced in LAIR-1-deficient mice, supporting an intrinsic function of LAIR-1 on neutrophils. Lair1-/- mouse model, RSV infection and cigarette smoke models, LAIR-1-Fc administration, intranasal CXCL1 challenge, cellular influx analysis Frontiers in immunology High 31080449
2015 A LAIR1 insertion in antibody genes generates broadly reactive antibodies against malaria RIFINs. The insertion, encoding the entire 98 amino acid collagen-binding domain of LAIR1, is inserted between the V and DJ segments via interchromosomal DNA transposition. Somatic mutations in the LAIR1 domain abolish collagen binding and increase binding to infected erythrocytes. The LAIR1 domain is both necessary and sufficient for RIFIN binding. Monoclonal antibody isolation, sequencing of antibody genes, domain deletion/mutation analysis, binding assays to infected erythrocytes and RIFIN antigens Nature High 26700814
2017 Crystal structure of the Fab fragment of a LAIR1-containing antibody was determined. The antigen-binding site positions the LAIR1 collagen-binding domain while the original Fab hypervariable loops are occluded, revealing a novel mechanism of antigen recognition in which the Fab acts as an adaptor linking the LAIR1 insert to constant antibody regions. X-ray crystallography of Fab fragment eLife High 28527239
2021 The structural basis of C1q collagen-like region (CLR) interaction with LAIR-1 was characterized. LAIR-1 interacts with C1q's CLR through a binding site close to but distinct from the C1r2s2 protease tetramer binding site. Site-directed mutagenesis identified LAIR-1 residues involved in C1q interaction. Recombinant protein production, binding assays, competition assays, site-directed mutagenesis International journal of molecular sciences Medium 34066122
2021 Crystal structures of two RIFINs in complex with LAIR1 were determined. The RIFIN-binding sites on LAIR1 overlap with the collagen-binding site. RIFINs engage LAIR1 with different binding angles. RIFIN activation of LAIR1 induces LAIR1-mediated cell signaling, and LAIR1-containing antibodies can block this pathway. X-ray crystallography of RIFIN-LAIR1 complexes, functional cell signaling assay, antibody blocking assay Cell reports High 34433057
2021 Structures of RIFIN-V2 domain in complex with LAIR1 domain were determined by crystallography. The LAIR1-binding region of RIFIN is hydrophobic and membrane-distal, exhibits extensive structural diversity, and interacts with RIFIN-V2 in a one-to-one fashion. Essential elements of RIFIN-binding on LAIR1 were identified. Negative-stain EM, X-ray crystallography, sequence/structure analysis Nature communications High 34244481
2018 LAIR-1 activation inhibits M1-like macrophage polarization and promotes alternative (M2) activation in human THP-1 macrophages. IFN-γ reduces LAIR-1 expression in THP-1 macrophages. IL-4 has no effect on LAIR-1 expression. THP-1 macrophage polarization model, cytokine treatment, LAIR-1 activation by cross-linking, phenotypic analysis Cellular immunology Medium 29887420
2018 Silencing LAIR-1 in THP-1 macrophages modulates the SHP-1/CREB/PPARγ pathway, promoting M2 macrophage polarization and increasing foam cell formation. LAIR-1 signaling through SHP-1 and CREB controls PPARγ expression and cholesterol metabolism. siRNA silencing of LAIR-1, western blotting for SHP-1/CREB activation, Oil Red O staining for foam cell formation, qPCR for PPARγ and cholesterol metabolism genes Cytokine Medium 30176557
2023 LAIR1 drives glioma progression through SHP2-mediated FAK nuclear localization, resulting in increased transcription of cyclin D1 and chemokines/cytokines (CCL5, TGFβ2, IL33). The LAIR1 ITIMs recruit SHP2, which interacts with FAK and induces FAK nuclear localization. LAIR1Y251/281F (ITIMs mutant) and SHP2Q510E mutants significantly reduced FAK nuclear localization and target gene expression. Co-immunoprecipitation, nuclear/cytoplasm fractionation, ITIM mutagenesis, in vitro and in vivo glioma growth assays Cell death & disease Medium 37845206
2021 Globular domain of adiponectin (gAdp) interacts with LAIR-1. In vitro experiments showed that gAdp inhibits T cell activation via LAIR-1 through a process involving downstream SHP-2. Pulldown/binding assay, T cell activation inhibition assay, SHP-2 downstream signaling analysis Biochemical and biophysical research communications Medium 34403808
2017 C1q can crosslink CD33 and LAIR-1 simultaneously and concurrently activate both inhibitory motifs. The globular region of C1q binds CD33, while the collagen-like region binds LAIR-1. Sialic acid masking of CD33 C2 domains regulates C1q-CD33 interactions. Binding assays, ITIM phosphorylation assay, siRNA-mediated knockdown, competition experiments with C1q domains Scientific reports Medium 28325905
2013 LAIR-1 inhibits osteoclastogenesis. Anti-LAIR-1 antibody treatment inhibits multinucleated osteoclast formation from mouse bone marrow cells in vitro. LAIR-1 overexpression in CD14+ monocytes also inhibits human osteoclastogenesis in vitro. Anti-LAIR-1 antibody treatment of bone marrow cultures, LAIR-1 overexpression in human monocytes, osteoclast differentiation assay Clinics (Sao Paulo, Brazil) Medium 23778340
2014 Trophoblasts and decidual stromal cells regulate decidual NK cell function via secretion of collagen, which interacts with LAIR-1 on dNKs. Co-culture of dNKs with HTR-8/DSCs upregulates LAIR-1 and decreases perforin expression and Th1-type cytokine production. These effects are abrogated by LAIR-2 (competitive LAIR-1 inhibitor) and by collagen knockdown via shRNA. Co-culture assay, flow cytometry, ELISA for cytokines, shRNA knockdown of collagen, LAIR-2 competition assay American journal of reproductive immunology Medium 24548186
2023 LAIR-1 agonism by a therapeutic antibody (NC525) induces cell death of leukemic stem cells (LSCs) but not healthy hematopoietic stem cells. LAIR-1 agonism drives a unique apoptotic signaling program in leukemic cells, enhanced in the presence of collagen. Anti-LAIR-1 agonist antibody treatment, cell viability assays, cell-derived and patient-derived xenograft models, apoptosis signaling analysis The Journal of clinical investigation High 37966113
2024 In HEL cells with JAK2 V617F mutation, LAIR-1 engagement with collagen recruits SHP-2, which downregulates tyrosine phosphorylation of JAK2, STAT1, STAT3, STAT5, AKT, and mTOR, thereby inhibiting cell proliferation and promoting apoptosis. Co-immunoprecipitation, western blotting for phosphorylation of pathway components, CCK-8 proliferation assay, flow cytometry apoptosis assay Xi bao yu fen zi mian yi xue za zhi Medium 38512030
2024 LAIR1 increases PD-L1 expression in HCC cells through the GSK-3β/β-catenin/MYC/PD-L1 pathway, inducing exhaustion of infiltrating CD8+ T cells. LAIR1 in HCC cells induces phosphorylation of GSK-3β, impairing β-catenin expression and nuclear localization, thereby reducing MYC-mediated PD-L1 suppression and ultimately upregulating PD-L1. Western blot, immunofluorescence, nucleus/cytoplasm fractionation, co-culture of HCC cells with CD8+ T cells, flow cytometry for T cell exhaustion markers Cellular signalling Medium 38199599
2025 MARCO is a ligand for LAIR-1. MARCO interacts with LAIR-1 in trans on NK cells and induces LAIR-1 inhibitory signaling. MARCO and LAIR-1 also interact in cis on THP-1 macrophages (demonstrated by single-molecule fluorescence microscopy), reducing LAIR-1 binding to collagen and dampening LAIR-1 signaling. CRISPR-Cas9 knockout of MARCO in IL-10-polarized macrophages increases LAIR-1-mediated inhibitory function. Binding assays, LAIR-1 signaling assay on NK cells, single-molecule fluorescence microscopy, CRISPR-Cas9 knockout, collagen binding assay Science signaling High 41364749
2024 LAIR1 in HCC cells promotes migration and invasion through the AKT-IKKβ-p65 axis. LAIR1 also induces alternative activation and infiltration of tumor-associated macrophages via upregulation of IL-6 and CCL5 within this axis. Transwell/scratch migration assay, transcriptome sequencing, western blot, nucleus/cytoplasm fractionation, ELISA, cytokine microarray Molecular carcinogenesis Medium 39016636
2024 LAIR-1 and PECAM-1 act to inhibit GPVI-mediated platelet activation via the same signaling pathway. LAIR-1/PECAM-1 double KO mice show platelets equally hyperresponsive to collagen as single KO mice. The enhanced Src family kinase activation previously shown in LAIR-1-deficient single KO mice is absent in DKO mice, suggesting functional redundancy through a shared pathway. LAIR-1/PECAM-1 double knockout mouse model, platelet aggregometry, flow cytometry, western blotting for Src signaling, FeCl3 thrombosis model Research and practice in thrombosis and haemostasis High 39318773
2025 PTIC (polymerized type I collagen) binds LAIR1 with affinity similar to collagen (confirmed by surface plasmon resonance). PTIC engagement of LAIR1 downregulates pSTAT1 (Tyr701) in IFN-γ-induced M1 macrophages, and reduces Mo1 monocyte subsets and associated cytokines in COVID-19 patients. Surface plasmon resonance binding assay, western blotting for pSTAT1, flow cytometry, clinical sample analysis International journal of molecular sciences Medium 39940787
2024 In fibrotic disease (systemic sclerosis), fibroblasts deposit disorganized collagen products that are dysfunctional LAIR-1 ligands, due to matrix metalloproteinase and PDGFR-dependent collagen remodeling. LAIR-1-deficient mice show increased skin fibrosis in two models, demonstrating that LAIR-1 is an essential negative feedback mechanism for tissue repair. LAIR-1 KO mouse models (repeated injury and bleomycin), fibroblast collagen deposition assay, MMP and PDGFR inhibitor experiments, LAIR-1 binding to patient-derived fibroblast matrix Journal of autoimmunity High 38696927
2020 LAIR-1 suppresses ovarian cancer cell growth by inhibiting the PI3K-AKT-mTOR axis. Co-IP and mass spectrometry identified potential LAIR-1-binding proteins including eukaryotic translation initiation factors, suggesting LAIR-1 may also regulate protein synthesis at the translational level. LAIR-1 overexpression in SKOV3 cells, proliferation/migration/apoptosis assays, western blotting for PI3K/AKT/mTOR, Co-IP with mass spectrometry, in vivo tumor model Aging Medium 32628130
2018 TNF-α stimulation causes shedding of cell-surface LAIR-1 from fibroblast-like synoviocytes via serine proteases. This shedding can be blocked by serine protease inhibitors. LAIR-1 overexpression in FLS reduces invasion and decreases mRNA levels of IL-6, IL-8, and MMP-13 in the presence of TNF-α. Flow cytometry for membrane LAIR-1, protease inhibitor experiments, qPCR, transwell invasion assay Clinical and experimental immunology Medium 29328500
2024 LAIR-1 inhibition (KO, antibody blockade, or 3-in-1 CAR) uncovered a LAIR1/factor XIII A/collagen IV immunosuppressive pathway across cancer types. LAIR1 inhibition induced phenotypic shift of M2-like macrophages toward M1 and enhanced CD8+ memory T cell populations, normalized tumor collagen IV in the TME. LAIR-1 KO mice, anti-LAIR-1 antibody blockade, 3-in-1 CAR T cell design, tumor models, flow cytometry, pathway analysis The Journal of clinical investigation Medium 40591413

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Collagen promotes anti-PD-1/PD-L1 resistance in cancer through LAIR1-dependent CD8+ T cell exhaustion. Nature communications 333 32908154
1997 LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes. Immunity 332 9285412
2006 Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1. The Journal of experimental medicine 268 16754721
2007 The inhibitory collagen receptor LAIR-1 (CD305). Journal of leukocyte biology 233 18063695
2012 C1q limits dendritic cell differentiation and activation by engaging LAIR-1. Proceedings of the National Academy of Sciences of the United States of America 142 23093673
2015 A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens. Nature 134 26700814
2008 The soluble leukocyte-associated Ig-like receptor (LAIR)-2 antagonizes the collagen/LAIR-1 inhibitory immune interaction. Journal of immunology (Baltimore, Md. : 1950) 122 18209062
2015 The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development. Nature cell biology 118 25915125
2022 Remodeling the tumor microenvironment via blockade of LAIR-1 and TGF-β signaling enables PD-L1-mediated tumor eradication. The Journal of clinical investigation 110 35230974
2017 Public antibodies to malaria antigens generated by two LAIR1 insertion modalities. Nature 93 28847005
2011 Tumor-expressed collagens can modulate immune cell function through the inhibitory collagen receptor LAIR-1. Molecular immunology 88 21955987
1999 Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is differentially expressed during human B cell differentiation and inhibits B cell receptor-mediated signaling. European journal of immunology 87 10540327
1998 p40/LAIR-1 regulates the differentiation of peripheral blood precursors to dendritic cells induced by granulocyte-monocyte colony-stimulating factor. European journal of immunology 76 9692876
2005 Inhibitory receptors CD85j, LAIR-1, and CD152 down-regulate immunoglobulin and cytokine production by human B lymphocytes. Clinical and diagnostic laboratory immunology 73 15939744
2005 The inhibitory leukocyte-associated Ig-like receptor-1 (LAIR-1) is expressed at high levels by human naive T cells and inhibits TCR mediated activation. Molecular immunology 71 15950745
2022 Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma. International journal of molecular sciences 68 36293412
2010 The immune inhibitory receptor LAIR-1 is highly expressed by plasmacytoid dendritic cells and acts complementary with NKp44 to control IFNα production. PloS one 67 21151495
2021 Homeostatic functions of monocytes and interstitial lung macrophages are regulated via collagen domain-binding receptor LAIR1. Immunity 60 34260887
2009 Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI. Blood 60 20007810
2007 Regulated expression of the inhibitory receptor LAIR-1 on human peripheral T cells during T cell activation and differentiation. European journal of immunology 60 17330824
2011 Enhanced secretion of leukocyte-associated immunoglobulin-like receptor 2 (LAIR-2) and soluble LAIR-1 in rheumatoid arthritis: LAIR-2 is a more efficient antagonist of the LAIR-1-collagen inhibitory interaction than is soluble LAIR-1. Arthritis and rheumatism 55 22127695
2015 C1q-mediated repression of human monocytes is regulated by leukocyte-associated Ig-like receptor 1 (LAIR-1). Molecular medicine (Cambridge, Mass.) 53 25247291
2017 Evidence for C1q-mediated crosslinking of CD33/LAIR-1 inhibitory immunoreceptors and biological control of CD33/LAIR-1 expression. Scientific reports 49 28325905
2020 Cancer immunotherapy based on blocking immune suppression mediated by an immune modulator LAIR-1. Oncoimmunology 42 33457088
2019 LAIR-1 Limits Neutrophilic Airway Inflammation. Frontiers in immunology 39 31080449
2013 The role of LAIR-1 (CD305) in T cells and monocytes/macrophages in patients with rheumatoid arthritis. Cellular immunology 39 24380839
2021 LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity. The Journal of allergy and clinical immunology 36 34144112
2014 Clinical significance of LAIR1 (CD305) as assessed by flow cytometry in a prospective series of patients with chronic lymphocytic leukemia. Haematologica 36 24415628
2014 Trophoblasts and decidual stromal cells regulate decidual NK cell functions via interaction between collagen and LAIR-1. American journal of reproductive immunology (New York, N.Y. : 1989) 35 24548186
2018 LAIR-1 activation inhibits inflammatory macrophage phenotype in vitro. Cellular immunology 34 29887420
2022 LAIR1, an ITIM-Containing Receptor Involved in Immune Disorders and in Hematological Neoplasms. International journal of molecular sciences 33 36555775
2004 Establishment of an ELISA system for determining soluble LAIR-1 levels in sera of patients with HFRS and kidney transplant. Journal of immunological methods 32 15350516
2022 Blocking LAIR1 signaling in immune cells inhibits tumor development. Frontiers in immunology 31 36211388
2017 Mice Lacking the Inhibitory Collagen Receptor LAIR-1 Exhibit a Mild Thrombocytosis and Hyperactive Platelets. Arteriosclerosis, thrombosis, and vascular biology 31 28336561
2022 Understanding the contextual functions of C1q and LAIR-1 and their applications. Experimental & molecular medicine 30 35562585
2018 Clinicopathologic significance of LAIR-1 expression in hepatocellular carcinoma. Current problems in cancer 30 29776595
2009 New assay to detect low-affinity interactions and characterization of leukocyte receptors for collagen including leukocyte-associated Ig-like receptor-1 (LAIR-1). European journal of immunology 29 19283782
2014 Simultaneous changes in serum HMGB1 and IFN-α levels and in LAIR-1 expression on plasmatoid dendritic cells of patients with juvenile SLE. New therapeutic options? Lupus 27 24399813
2003 9.1C3 is identical to LAIR-1, which is expressed on hematopoietic progenitors. Biochemical and biophysical research communications 27 14559247
2024 Lupus autoantibodies initiate neuroinflammation sustained by continuous HMGB1:RAGE signaling and reversed by increased LAIR-1 expression. Nature immunology 26 38448779
2018 LAIR-1 overexpression and correlation with advanced pathological grade and immune suppressive status in oral squamous cell carcinoma. Head & neck 26 30549148
2023 LAIR-1 agonism as a therapy for acute myeloid leukemia. The Journal of clinical investigation 25 37966113
2020 LAIR-1 suppresses cell growth of ovarian cancer cell via the PI3K-AKT-mTOR pathway. Aging 22 32628130
2020 Role and mechanism of LAIR-1 in the development of autoimmune diseases, tumors, and malaria: A review. Current research in translational medicine 22 32690423
2022 A perspective on LILRBs and LAIR1 as immune checkpoint targets for cancer treatment. Biochemical and biophysical research communications 21 36344166
2018 Silencing LAIR-1 in human THP-1 macrophage increases foam cell formation by modulating PPARγ and M2 polarization. Cytokine 21 30176557
2018 Collagen type I degradation fragments act through the collagen receptor LAIR-1 to provide a negative feedback for osteoclast formation. Bone 21 30217615
2021 Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19: Anti-IFN antibodies in critical COVID-19 correlate with poor ISG response and upregulation of LAIR1 surface protein in PBMCs. bioRxiv : the preprint server for biology 20 33758859
2003 Chronic active Epstein-Barr virus infection associated with low expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) on natural killer cells. Journal of clinical immunology 19 12757266
2023 LAIR-1 limits macrophage activation in acute inflammatory lung injury. Mucosal immunology 18 37634572
2020 LAIR-1 overexpression inhibits epithelial-mesenchymal transition in osteosarcoma via GLUT1-related energy metabolism. World journal of surgical oncology 18 32563267
2017 Incorporation of a Ligand Peptide for Immune Inhibitory Receptor LAIR-1 on Biomaterial Surfaces Inhibits Macrophage Inflammatory Responses. Advanced healthcare materials 18 29083540
2013 Expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) on osteoclasts and its potential role in rheumatoid arthritis. Clinics (Sao Paulo, Brazil) 18 23778340
2023 A novel mechanism of cannabidiol in suppressing ovarian cancer through LAIR-1 mediated mitochondrial dysfunction and apoptosis. Environmental toxicology 16 36810933
2019 Expression of LAIR-1 (CD305) on Human Blood Monocytes as a Marker of Hepatic Cirrhosis Progression. Journal of immunology research 16 31019980
2019 Signal inhibitory receptor on leukocytes (SIRL)-1 and leukocyte- associated immunoglobulin-like receptor (LAIR)-1 regulate neutrophil function in infants. Clinical immunology (Orlando, Fla.) 16 31843567
2021 Molecular Basis of Complement C1q Collagen-Like Region Interaction with the Immunoglobulin-Like Receptor LAIR-1. International journal of molecular sciences 14 34066122
2019 Molecular basis of reduced LAIR1 expression in childhood severe malarial anaemia: Implications for leukocyte inhibitory signalling. EBioMedicine 14 31257148
2017 The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition. eLife 14 28527239
2023 LAIR1 drives glioma progression by nuclear focal adhesion kinase dependent expressions of cyclin D1 and immunosuppressive chemokines/cytokines. Cell death & disease 13 37845206
2021 1,25-Dihydroxyvitamin D3 and 20-Hydroxyvitamin D3 Upregulate LAIR-1 and Attenuate Collagen Induced Arthritis. International journal of molecular sciences 13 34948139
2021 Adiponectin's globular domain inhibits T cell activation by interacting with LAIR-1. Biochemical and biophysical research communications 12 34403808
2018 LAIR-1 shedding from human fibroblast-like synoviocytes in rheumatoid arthritis following TNF-α stimulation. Clinical and experimental immunology 12 29328500
2021 Structural basis of malarial parasite RIFIN-mediated immune escape against LAIR1. Cell reports 11 34433057
2019 C1q contributes to post-stroke angiogenesis via LAIR1-HIF1α-VEGF pathway. Frontiers in bioscience (Landmark edition) 11 30844729
2024 LAIR1-mediated resistance of hepatocellular carcinoma cells to T cells through a GSK-3β/β-catenin/MYC/PD-L1 pathway. Cellular signalling 10 38199599
2024 Antitumor Activity of a Novel LAIR1 Antagonist in Combination with Anti-PD1 to Treat Collagen-Rich Solid Tumors. Molecular cancer therapeutics 10 38648067
2019 Integrated OMICS platforms identify LAIR1 genetic variants as novel predictors of cross-sectional and longitudinal susceptibility to severe malaria and all-cause mortality in Kenyan children. EBioMedicine 10 31278068
2005 Identification and characterization of the rat homologue of LAIR-1. Immunogenetics 10 15902436
2025 Inhibitory pattern recognition receptors: lessons from LAIR1. Nature reviews. Immunology 7 40425821
2024 LPS and type I and II interferons have opposing effects on epigenetic regulation of LAIR1 expression in mouse and human macrophages. Journal of leukocyte biology 6 38011310
2023 Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis. Arthritis research & therapy 6 38062469
2018 Low Expression of Leucocyte Associated Immunoglobulin Like Receptor-1 (LAIR-1/CD305) in a Cohort of Pediatric Acute Lymphoblastic Leukemia Cases. Asian Pacific journal of cancer prevention : APJCP 6 30486600
2025 Polymerized Type I Collagen Downregulates STAT-1 Phosphorylation Through Engagement with LAIR-1 in Circulating Monocytes, Avoiding Long COVID. International journal of molecular sciences 5 39940787
2025 Targeting immune checkpoint LAIR1 with antibody blockade or 3-in-1 CAR T cells enhances antitumor response. The Journal of clinical investigation 5 40591413
2024 LAIR1 promotes hepatocellular carcinoma cell metastasis and induces M2-macrophage infiltration through activating AKT-IKKβ-p65 axis. Molecular carcinogenesis 5 39016636
2024 LAIR-1 and PECAM-1 function via the same signaling pathway to inhibit GPVI-mediated platelet activation. Research and practice in thrombosis and haemostasis 5 39318773
2024 Leukemic B cells expression of CD200 and Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, CD305) in Chronic Lymphocytic Leukemia patients in relation to Treg frequency. Pathology, research and practice 5 39471525
2021 Structural basis of LAIR1 targeting by polymorphic Plasmodium RIFINs. Nature communications 5 34244481
2014 Comparison of LAIR-1 genetic pathways in murine vs human internal organs. Gene 5 25234728
2024 Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis. Journal of autoimmunity 4 38696927
2023 Effects of LAIR-1 on hepatocellular carcinoma cell proliferation and invasion via PI3K-AKT-mTOR pathway regulation. Immunity, inflammation and disease 4 37647449
2025 Targeting LAIR1-mediated immunosuppression adds a new weapon to our immunotherapy arsenal. The Journal of clinical investigation 3 40829176
2024 Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is reduced with preeclampsia and small for gestational aged fetuses. Placenta 3 39216164
2024 Ulcerative Colitis, LAIR1 and TOX2 Expression, and Colorectal Cancer Deep Learning Image Classification Using Convolutional Neural Networks. Cancers 3 39766129
2008 [The up-regulated expression of LAIR-1 in tumor patients PBMC]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 3 18394348
2007 Generation of rat monoclonal antibodies against murine LAIR-1. Hybridoma (2005) 3 17979548
2024 LAIR1 prevents excess inflammatory tissue damage in S. aureus skin infection and Cutaneous T-cell Lymphoma. bioRxiv : the preprint server for biology 2 38915487
2024 A new mechanism of antibody diversity: formation of the natural antibodies containing LAIR1 and LILRB1 extracellular domains. Antibody therapeutics 2 38933531
2014 A non-stimulatory monoclonal antibody against the inhibitory immunoreceptor LAIR-1. Monoclonal antibodies in immunodiagnosis and immunotherapy 2 24694245
2025 Development of an anti-LAIR1 antibody-drug conjugate for acute myeloid leukemia therapy. International journal of biological macromolecules 1 39753170
2025 The Role of LAIR1 as a Regulatory Receptor of Antitumor Immune Cell Responses and Tumor Cell Growth and Expansion. Biomolecules 1 40563506
2025 The scavenger receptor MARCO is a ligand for the immune inhibitory receptor LAIR-1 and regulates its function in cis. Science signaling 1 41364749
2024 [leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) inhibits proliferation and promotes apoptosis of human HEL cells with JAK2 V617F mutation by blocking the JAK/STAT and PI3K/AKT signaling pathways]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 38512030
2024 Utility of leukocyte-associated immunoglobulin-like receptor-1 (CD305) in flow cytometric detection of minimal bone marrow involvement by B-cell non-Hodgkin lymphoma. Cytometry. Part B, Clinical cytometry 1 39031805
2024 CD305 participates in abnormal activation of memory CD4+ T cells in patients with RA and attenuates collagen-induced arthritis. Molecular immunology 1 39079337
2025 Intraepithelial Lymphocytes and LAIR1 Expression in Celiac Disease. Biomedicines 0 41153806
2025 LAIR1 prevents excess inflammatory tissue damage in Staphylococcus aureus skin infection and Cutaneous T-cell Lymphoma. JCI insight 0 41231542
2023 Lupus autoantibodies initiate a maladaptive equilibrium sustained by HMGB1:RAGE signaling and reversed by LAIR-1:C1q signaling. Research square 0 37292843
2005 [Identification of cell lines expressing the putative ligand(s) for LAIR-1(CD305) and LAIR-2(CD306)]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 16143055

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