Affinage

Showing ITGALLFA-1 is a alias.

ITGAL

Integrin alpha-L · UniProt P20701

Length
1170 aa
Mass
128.8 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 34 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

ITGAL encodes the alpha-L subunit (CD11a) that pairs with CD18 to form the beta2-integrin LFA-1, a central mediator of leukocyte adhesion, immune cell collaboration, and activation (PMID:2809204, PMID:1670945). LFA-1 binds a family of immunoglobulin-superfamily counter-receptors through its CD11a I-domain: ICAM-1 (PMID:2809204), ICAM-2 (via the first Ig domain) (PMID:1346150, PMID:8349630), the neuronal ligand telencephalin/ICAM-5 (first Ig domain required) (PMID:8993013, PMID:10741396), and the soluble endothelial factor ESM-1, which binds with high affinity and competes with ICAM-1 (PMID:11544294). Crystal and NMR structures of the I-domain established that cation dependence of ligand binding does not arise from metal-induced conformational change of the I-domain itself, and revealed an allosteric pocket where lovastatin binds to inhibit LFA-1/ICAM-1 engagement (PMID:8805579, PMID:10493852). LFA-1 adhesiveness is controlled by inside-out signaling downstream of antigen-receptor and costimulatory inputs: TCR/CD3 crosslinking drives PKC-dependent association of CD11a/CD18 with the actin cytoskeleton (PMID:1346786), the Src-family kinase Lck is required for CD11a/CD18 surface expression and ICAM-1 adhesion (PMID:12115650), and CD40 signaling activates LFA-1-mediated homotypic adhesion in B cells (PMID:1706378). Functional engagement of LFA-1 enhances T-cell cytokine output and supports T cell-B cell collaboration and costimulation (PMID:1670945, PMID:1346150, PMID:8098668). ITGAL transcription is restricted to leukocytes through cell-type-specific proximal promoter elements and is driven in myeloid cells by RUNX/AML and C/EBP factors at the MS7 element (PMID:8097887, PMID:12855590), while DNA methylation of promoter-flanking sequences enforces tissue-restricted and quantitative control: this repressive state is maintained by RFX1-recruited DNMT1/HDAC1/SUV39H1 and by H3K27 trimethylation, and is reversed by JMJD3-mediated demethylation, with aberrant hypomethylation driving CD11a overexpression in lupus and aging T cells (PMID:12115234, PMID:12036881, PMID:20223637, PMID:21192791, PMID:28430662). In vivo, CD11a directs neutrophil penetration of the endothelium during extravasation (PMID:10648403, PMID:30967528), CD8+ T cell effector differentiation and adipose-tissue infiltration (PMID:24158516, PMID:23357382), glioma-associated microglia motility and glioma growth (PMID:34043012), and host responses in ischemic brain injury and Salmonella infection (PMID:24130503, PMID:31636138), and its loss prevents autoimmune diabetes by impairing T cell activation rather than trafficking (PMID:19223596).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1989 High

    Established the founding adhesive function of LFA-1 by showing CD11a/CD18 mediates leukocyte adhesion to endothelium specifically through ICAM-1, distinct from CD11b/CD18.

    Evidence Monoclonal antibody blocking of PMN-endothelial adhesion with additive-inhibition analysis and surface down-modulation assays

    PMID:2809204

    Open questions at the time
    • Does not define the I-domain residues contacting ICAM-1
    • Does not address activation state of the integrin
  2. 1991 High

    Demonstrated that LFA-1 adhesion is actively induced by immune signaling, linking CD40 and TCR-dependent T cell-B cell interactions to functional adhesion and B cell responses.

    Evidence B cell aggregation assays with CD40 truncation mutants and anti-CD18 blockade; T-B collaboration assays with anti-CD11a/CD18 blockade and IL-2 rescue

    PMID:1670945 PMID:1706378

    Open questions at the time
    • Intracellular signaling pathway from CD40 to LFA-1 not resolved
    • Does not identify the ligand on the partner cell biochemically
  3. 1992 High

    Identified ICAM-2 as a second counter-receptor that delivers costimulatory signals and showed TCR crosslinking drives PKC-dependent LFA-1 association with actin, defining inside-out activation.

    Evidence T cell proliferation with co-immobilized ICAM-2-Ig; fluorescence colocalization and cytoskeletal-fraction IP with PKC inhibition; CD11a-specific mAb-triggered aggregation

    PMID:1346150 PMID:1346786 PMID:1352499

    Open questions at the time
    • Identity of cytoskeletal adaptors linking LFA-1 to actin not defined
    • Direct PKC substrate on the integrin tail not established
  4. 1993 High

    Mapped the ICAM-2 binding region to its first Ig domain and defined the leukocyte-restricted, cell-type-specific architecture of the ITGAL promoter.

    Evidence Synthetic-peptide binding to purified CD11a/CD18 with adhesion inhibition; promoter deletion/reporter mapping and EMSA in lymphoid vs myeloid cell lines; cytokine mRNA induction assays

    PMID:8097887 PMID:8098668 PMID:8099450 PMID:8103515 PMID:8349630

    Open questions at the time
    • Specific trans-acting factors at proximal elements not all identified
    • Negative regulatory region between -880 and -226 mechanistically uncharacterized
  5. 1996 High

    Resolved that I-domain cation dependence is not explained by metal-induced I-domain rearrangement, refining the structural basis of ligand binding.

    Evidence X-ray crystallography of the CD11a I-domain with Mg2+ and metal-free, compared to Mn2+-bound structure

    PMID:8805579

    Open questions at the time
    • Quaternary integrin rearrangement on activation not visualized
    • Does not capture ligand-bound I-domain conformation
  6. 1997 High

    Extended LFA-1's ligand repertoire to the nervous system by identifying telencephalin/ICAM-5 as a CD11a/CD18 ligand, later mapped to its first Ig domain.

    Evidence Adhesion of leukocytes to recombinant TLN and reciprocal binding of TLN-transfected cells; domain-deletion constructs and T cell binding to hippocampal neurons

    PMID:10741396 PMID:8993013

    Open questions at the time
    • Physiological context of leukocyte-neuron LFA-1/ICAM-5 binding not defined
    • Affinity relative to ICAM-1/ICAM-2 not quantified
  7. 1999 High

    Defined a druggable allosteric site by determining lovastatin binds the I-domain to inhibit LFA-1/ICAM-1, distinct from competitive blockade.

    Evidence NMR and X-ray crystallography of the lovastatin-I-domain complex with functional inhibition assays

    PMID:10493852

    Open questions at the time
    • In vivo relevance of statin binding to LFA-1 not addressed
    • Allosteric coupling to ligand site not structurally traced
  8. 2000 High

    Dissected the kinetics of adhesion, showing LFA-1 mediates initial neutrophil capture while constitutive activation can arise from beta2 cytoplasmic-region truncation.

    Evidence Shear-flow capture/aggregation assays with selective antibody blockade; transfection of truncated beta2 variants with mAb 24 activation-epitope detection

    PMID:10648403 PMID:10946284

    Open questions at the time
    • Mechanism by which beta2 truncation triggers constitutive activation not resolved
    • Capture/stabilization handoff between LFA-1 and Mac-1 not molecularly defined
  9. 2001 High

    Identified ESM-1 as a soluble high-affinity LFA-1 ligand that competes with ICAM-1, implying a regulatory mode of adhesion control.

    Evidence Biacore SPR kinetics (Kd 18.7 nM), reciprocal co-IP with anti-CD11a/CD18, and ICAM-1 competition assays

    PMID:11544294

    Open questions at the time
    • Physiological/in vivo role of ESM-1 antagonism of LFA-1 not established
    • Binding site on the I-domain not mapped
  10. 2002 High

    Established that DNA methylation of ITGAL promoter-flanking sequences functionally and quantitatively controls CD11a expression, and that this is dysregulated in lupus and aging; Lck was shown to be required for CD11a/CD18 surface expression and activation.

    Evidence Bisulfite sequencing, patch-methylation reporter assays, DNase-I sensitivity, and azacytidine treatment in lupus, fibroblast, and aging T cell systems; Lck-deficient Jurkat line with PP2 inhibition and Lck rescue

    PMID:12020947 PMID:12036881 PMID:12115234 PMID:12115650

    Open questions at the time
    • Trans-acting machinery maintaining methylation not yet identified at this stage
    • How Lck loss blocks CD11a/CD18 surface assembly mechanistically unresolved
  11. 2003 High

    Defined transcription-factor control of CD11a in myeloid cells via RUNX/AML and C/EBP at the MS7 element, explaining repression by AML1/ETO, and showed Ly6C-triggered LFA-1 clustering augments adhesion.

    Evidence ChIP, EMSA, MS7-mutant reporters, and RUNX/CBFbeta overexpression with surface flow cytometry; Ly6C crosslinking with cytoskeletal and calpain inhibitors in a flow-adhesion assay

    PMID:12538687 PMID:12855590

    Open questions at the time
    • Interplay between RUNX/C/EBP control and DNA methylation not integrated
    • Direct signaling intermediates of Ly6C-to-LFA-1 clustering not defined
  12. 2010 High

    Identified the repressive chromatin machinery, showing RFX1 recruits DNMT1, HDAC1, and SUV39H1 to maintain ITGAL methylation and H3K9me3, with loss driving lupus CD11a overexpression.

    Evidence ChIP for H3K9me3, RFX1-SUV39H1 co-IP, and RFX1 gain/loss-of-function in SLE vs control CD4+ T cells

    PMID:20223637 PMID:21192791

    Open questions at the time
    • Upstream cause of RFX1 downregulation in SLE not established
    • Relative contribution of each recruited enzyme not separated
  13. 2013 High

    Defined non-redundant in vivo roles of CD11a in CD8+ T cell effector differentiation and adipose infiltration, in ischemic neuroprotection, in polyamine-linked methylation control, and in T cell activation underlying autoimmune diabetes.

    Evidence CD11a/CD11b/CD11c knockout mice in Listeria infection and obesity with adoptive transfer; QTL mapping and ischemia models; DFMO/spermine manipulation of DNMT activity and ITGAL methylation; ItgaL-deficient NOD mice with transfer and endothelial adhesion assays

    PMID:19223596 PMID:23357382 PMID:23418509 PMID:24130503 PMID:24158516

    Open questions at the time
    • Tissue-specific ligand engagements driving each in vivo phenotype not all defined
    • How adhesion-independent CD11a contributes to T cell activation in diabetes unresolved
  14. 2017 High

    Added the H3K27 axis to ITGAL epigenetic control, showing JMJD3 demethylates the promoter to upregulate CD11a in lupus T cells.

    Evidence ChIP for H3K27me3 and JMJD3 with JMJD3 overexpression and siRNA in SLE and healthy CD4+ T cells

    PMID:28430662

    Open questions at the time
    • Trigger for increased JMJD3 recruitment in SLE not identified
    • Interplay between H3K27 and DNA-methylation control not integrated
  15. 2019 High

    Spatially resolved LFA-1's extravasation role and confirmed a genetic requirement in host defense, separating LFA-1 (endothelial penetration) from Mac-1 (basement-membrane transit) and establishing causal Itgal contribution to Salmonella susceptibility.

    Evidence LFA-1 and Mac-1 FRET knockin mice with two-photon intravital imaging and TEM; QTL mapping with quantitative complementation of an Itgal loss-of-function variant

    PMID:30967528 PMID:31636138

    Open questions at the time
    • Endothelial ligands distinguishing hotspot I from hotspot II not defined
    • Mechanism by which CD11a affects Salmonella defense unresolved
  16. 2022 High

    Revealed a cell-intrinsic CD11a program in glioma-associated microglia controlling CX3CR1 expression, CX3CL1-directed motility, CCL5 production, and tumor growth.

    Evidence CD11a-knockout microglia in vitro and anti-CD11a antibody treatment of Nf1 optic glioma mice with RNAScope/IHC and human-specimen validation

    PMID:34043012

    Open questions at the time
    • Signaling link from CD11a to Cx3cr1 transcription not defined
    • Ligand engaged by microglial CD11a in the glioma microenvironment unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct ligand engagements (ICAM-1/2, ICAM-5, ESM-1) are selected in specific tissues and how inside-out signaling, conformational activation, and ligand competition are integrated to produce the diverse in vivo functions of CD11a remains unresolved.
  • No unified model linking activation state to tissue-specific ligand choice
  • Mechanistic basis of adhesion-independent CD11a roles in T cell activation not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-168256 Immune System 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3
Complex memberships
LFA-1 (CD11a/CD18)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 CD11a/CD18 (LFA-1) mediates PMN adhesion to unstimulated endothelial cells by binding to ICAM-1; anti-CD11a and anti-ICAM-1 antibodies blocked the same ~50% of adhesion without additive effect, while CD11b/CD18 mediates adhesion via a distinct, non-ICAM-1 ligand. Interaction of CD11a/CD18 with surface-bound ICAM-1 caused selective down-modulation of CD11a/CD18 from the apical surface of macrophages. Monoclonal antibody blocking assays on PMN-endothelial cell adhesion; anti-ICAM-1 additive inhibition analysis; surface down-modulation on ICAM-1-coated surfaces Journal of immunology High 2809204
1991 CD40 signaling in B cells activates CD11a/CD18 (LFA-1)-mediated homotypic adhesion; this activation requires CD40 cytoplasmic tail-mediated signaling (cells expressing CD40 lacking the cytoplasmic tail did not aggregate), is energy- and cation-dependent, and is blocked by anti-CD18 mAb. CD40 signaling also induces upregulation of ICAM-1 (CD54) on B cells. B cell aggregation assays with anti-CD40 mAb; comparison of full-length vs. cytoplasmic tail-truncated CD40-transfected mouse B cell lines; inhibitor studies (RNA/protein synthesis, anti-CD18 mAb) Journal of immunology High 1706378
1991 CD11a/CD18:ICAM-1 interactions are required for T cell–B cell collaboration leading to B cell proliferation and differentiation; anti-CD11a or anti-CD18 mAbs blocked B cell responses without directly inhibiting T cell DNA synthesis or IL-2 production, indicating CD11a on resting B cells interacts with ICAM-1 on activated CD4+ T cells. B cell proliferation/differentiation assays with blocking mAbs; T cell-independent activation controls; LFA-1-negative T cell clone controls; exogenous IL-2 rescue experiments Journal of immunology High 1670945
1992 ICAM-2 serves as a second counter-receptor for CD11a/CD18 and provides T cell costimulatory signals; soluble ICAM-2-Ig fusion protein co-immobilized with anti-TCR mAb induced CD4+ T cell proliferation and IL-2R expression, and this costimulatory effect was almost completely inhibited by anti-CD11a or anti-CD18 mAbs. T cell proliferation assays with co-immobilized ICAM-2-Rg and anti-TCR mAb; blocking with anti-CD11a and anti-CD18 mAbs; CD25 expression analysis Journal of immunology High 1346150
1992 TCR complex crosslinking induces PKC-dependent association of CD11a/CD18 with the actin cytoskeleton; anti-CD3 mAb induced actin polymerization, colocalization of F-actin with LFA-1 by fluorescence microscopy, and LFA-1 immunoprecipitation from detergent-insoluble cytoskeletal fractions. This was blocked by the PKC inhibitor staurosporine or PKC desensitization, and accompanied by transient CD11a hyperphosphorylation. Fluorescence microscopy colocalization; immunoprecipitation from detergent-insoluble cytoskeletal fraction; PKC inhibitor (staurosporine); PKC desensitization; beta2-deficient T cell controls The Journal of cell biology High 1346786
1992 Triggering of CD11a (LFA-1 alpha chain) by specific mAbs, but not anti-LFA-1 beta chain mAbs, induces homotypic adhesion in pre-activated (but not resting) T cells via LFA-1 itself; this requires an intact cytoskeleton (inhibited by cytochalasin B) and is sensitive to H7 (PKC/PKA inhibitor), implicating cytoskeletal reorganization and kinase signaling in LFA-1 alpha chain-mediated inside-out signaling. T cell homotypic aggregation assays; blocking mAbs against CD11a, CD18, ICAM-1; cytochalasin B and H7 inhibitor studies; temperature and divalent cation dependence tests European journal of immunology Medium 1352499
1993 The CD11a gene promoter contains distinct cell-type-specific regulatory elements: the region -40 to -17 drives activity in T lymphocytes (Jurkat), and the first 17 bp relative to transcription start site drives activity in myeloid cells (HL-60); the 1.7 kb promoter is active only in leukocytes and not in non-leukocyte cell lines. Promoter cloning; transient expression assays with deletion reporter constructs in Jurkat, HL-60, and non-leukocyte cell lines Proceedings of the National Academy of Sciences Medium 8097887
1993 The CD11a promoter contains a 'LYM' box binding lymphoid/preerythroid and myeloid cell-specific DNA-binding activities, and a 'GAGA' sequence (RRRGAGGAAG) binding MS-1 (myeloid-specific, likely Ets family) and MS-2 (broadly expressed but developmentally regulated in myeloid cells), which control myeloid and lymphoid expression of CD11a. Promoter cloning and characterization; DNA-protein binding assays (EMSA); transient expression assays in lymphoid and myeloid cell lines Proceedings of the National Academy of Sciences Medium 8099450
1993 A synthetic peptide from residues 21–42 of the first Ig domain of ICAM-2 binds directly to purified CD11a/CD18 and inhibits endothelial cell adhesion to this integrin, as well as B lymphoblastoid cell binding to endothelial cells, identifying the ICAM-2 D1 region as the CD11a/CD18 binding site. Direct binding of synthetic peptide to purified CD11a/CD18; adhesion inhibition assays; leukocyte binding to peptide-coated plastic The Journal of biological chemistry High 8349630
1993 CD11a/CD18 engagement enhances TNF-alpha and IL-2 mRNA expression (3- to 10-fold) in activated T cells; LFA-1-mediated homotypic aggregation and adhesion to ICAM-1 enhanced cytokine production, which was blocked by anti-CD11a, anti-CD18, or anti-ICAM-1 mAbs. Engagement of CD11a/CD18 on interaction with endothelial cells also enhanced cytokine production. Northern blot analysis of TNF-alpha mRNA; cytokine production assays; blocking with anti-CD11a, anti-CD18, anti-ICAM-1 mAbs; co-immobilized ICAM-1 adhesion assays Cellular immunology Medium 8098668
1993 CD11a promoter activity is negatively regulated by sequences between -880 and -226, while the proximal region shows tissue-specific activity; the major transcription initiation site resembles an 'initiator' sequence; the -880/+83 fragment confers tissue-specific expression to reporter genes in leukocyte vs. non-leukocyte cell lines. CD11a promoter isolation; identification of transcription start sites; transient reporter gene expression assays with deletion constructs in LFA1+ and LFA1- cell lines The Journal of biological chemistry Medium 8103515
1996 Crystal structures of the CD11a I-domain with no bound metal, bound Mg2+, and previously known Mn2+ show no major structural rearrangements at the metal-binding site; the cation-dependence of CD11a/CD18 ligand binding is therefore not explained by I-domain conformational change upon metal binding/removal, suggesting the metal ion participates directly in ligand contact or promotes favorable quaternary integrin arrangement. X-ray crystallography of CD11a I-domain with Mg2+ and without metal ion; structural comparison to previously solved Mn2+-bound structure Structure High 8805579
1997 Telencephalin (TLN/ICAM-5), a neuronal glycoprotein with NH2-terminal Ig domains homologous to ICAMs, is a cellular ligand for CD11a/CD18; T cells and B lymphoblastoid cells bound to immunopurified recombinant TLN via CD11a/CD18, and TLN-transfected L cells bound purified CD11a/CD18; binding was inhibited by anti-CD11a/CD18 antibody. Cell adhesion assays to immunopurified recombinant TLN; reciprocal binding of TLN-transfected L cells to purified CD11a/CD18; antibody blocking; domain deletion analysis Journal of immunology High 8993013
1999 Lovastatin binds to the I-domain of the CD11a alpha-chain, inhibiting LFA-1/ICAM-1 interaction; NMR spectroscopy and X-ray crystallography revealed the atomic details of lovastatin binding to the I-domain, representing an allosteric mechanism of LFA-1 inhibition distinct from ligand-competitive blocking. NMR spectroscopy; X-ray crystallography of lovastatin-I-domain complex; LFA-1/ICAM-1 interaction inhibition assays Journal of molecular biology High 10493852
2000 The first Ig domain of ICAM-5 (telencephalin) is required for CD11a/CD18 binding; protein constructs containing the first Ig domain supported CD11a/CD18 interaction, while deletion of the first domain abolished binding; mAbs against the first domain completely blocked interaction. T cell binding to rat hippocampal neurons was blocked by anti-CD11a/CD18 and anti-ICAM-5 mAbs. Domain deletion constructs of ICAM-5; binding assays to CD11a/CD18; monoclonal antibody blocking; human T cell binding to rat hippocampal neurons European journal of immunology High 10741396
2000 CD11a/CD18 mediates initial neutrophil capture to ICAM-1 under shear stress (formyl peptide stimulation boosted capture efficiency ~4-fold via CD11a/CD18), while CD11b/CD18 is required for stable aggregate formation over sustained shear; these are sequential, cooperative steps in neutrophil adhesion to ICAM-1. Cone-plate viscometer shear assays; two-color flow cytometry measurement of heterotypic aggregates; monoclonal antibody blockade of CD11a and CD11b; ICAM-1-transfected target cells Blood High 10648403
2000 Truncated beta2 subunit variants terminating after Q444 are sufficient for LFA-1 (CD11a/CD18) surface expression; surface-expressed LFA-1 variants with truncated beta2 are constitutively active for ICAM-1 adhesion and express the activation reporter epitope of mAb 24, indicating the major cysteine-rich region and conserved cysteines at 445/447/449 are not required for surface expression but their removal leads to constitutive activation. Transfection of truncated beta2 variants; flow cytometry for surface expression; ICAM-1 adhesion assays; mAb 24 activation epitope detection Journal of immunology Medium 10946284
2001 Endothelial cell-specific molecule-1 (ESM-1) binds directly to LFA-1 (CD11a/CD18) on lymphocytes, monocytes, and Jurkat cells; binding is divalent cation-dependent, saturable, and demonstrated by co-immunoprecipitation with anti-CD11a and anti-CD18 mAbs; real-time Biacore biosensor confirmed direct high-affinity interaction (Kd = 18.7 nM); ESM-1 dose-dependently inhibits soluble ICAM-1 binding to Jurkat cells. Co-immunoprecipitation with anti-CD11a and anti-CD18 mAbs; Biacore surface plasmon resonance kinetics; ICAM-1 competitive binding assay; Ca2+/Mg2+/Mn2+ dependence analysis Journal of immunology High 11544294
2002 Specific sequences flanking the ITGAL promoter (>500 bp 5' of transcription start site) are hypomethylated in lupus T cells and in T cells treated with 5-azacytidine or procainamide; patch methylation of this region suppresses ITGAL promoter function, demonstrating that DNA methylation changes at these sequences functionally regulate LFA-1 expression. Bisulfite sequencing of ITGAL promoter and flanking regions; patch methylation of promoter sequences in reporter constructs; T cells from lupus patients vs. healthy subjects Arthritis and rheumatism High 12115234
2002 DNA methylation and chromatin structure contribute to tissue-specific CD11a expression; ITGAL promoter and 5' flanking regions are heavily methylated in fibroblasts (which do not express CD11a) but not in T cells; methylation correlates with closed chromatin (DNase I resistance); patch methylation of promoter and flanking regions suppresses ITGAL promoter function; treatment of fibroblasts with methylation inhibitor decreased promoter methylation and increased CD11a mRNA. Bisulfite sequencing; DNase I sensitivity assay; patch methylation of reporter constructs; 5-azacytidine treatment of fibroblasts; CD11a mRNA measurement Blood High 12036881
2002 Lck tyrosine kinase is required for surface expression and activation of CD11a/CD18 in T cells; Lck-deficient Jurkat cells (JCaM1.6) showed dramatically reduced CD11a/CD18 surface expression, reduced CD3- and PMA-induced adhesion to ICAM-1, accumulation of immature (incompletely glycosylated) CD18 not associated with CD11a, and re-transfection of Lck restored adhesion. Src-family kinase inhibitor PP2 also inhibited CD3-induced adhesion at concentrations blocking MAP kinase pathway. Lck-deficient Jurkat cell line (JCaM1.6); PP2 kinase inhibitor; flow cytometry for surface expression; cell surface labeling; ICAM-1 adhesion assays; Lck reconstitution by transfection European journal of immunology High 12115650
2002 Age-dependent hypomethylation of sequences flanking the ITGAL promoter correlates with increased CD11a mRNA expression in aging T cells; CD11a mRNA increases with age and with experimentally induced DNA hypomethylation; patch methylation of this region suppresses promoter function; DNA methyltransferases 1 and 3a decrease with aging. Bisulfite sequencing; patch methylation of promoter sequences in reporter constructs; CD11a mRNA measurement by RT-PCR; DNA methyltransferase activity measurement Mechanisms of ageing and development Medium 12020947
2003 RUNX/AML and C/EBP factors regulate CD11a expression in myeloid cells through overlapping binding sites in the MS7 element of the CD11a promoter; C/EBP factors predominate in proliferating myeloid cells, while RUNX/AML factors (especially RUNX3/AML-2) bind in differentiated myeloid cells and increase CD11a/CD18 expression. AML-1/ETO inhibits CD11a promoter activity, explaining low CD11a/CD18 expression in t(8;21) myeloid leukemia cells. EMSA; ChIP; reporter gene assays with mutated MS7 elements; transfection of AML1B/CBFbeta and RUNX3; flow cytometry for CD11a/CD18 surface expression; comparison of myeloid cell lines and primary cells Blood High 12855590
2003 Ly6C cross-linking induces clustering of LFA-1 (CD11a/CD18) on CD8 T cell surfaces via a mechanism dependent on actin cytoskeleton reorganization and calpain (intracellular protease) activity, but not PI3-kinase; LFA-1 clustering augments lymphocyte adhesion to endothelium in a capillary flow assay, and this is blocked by anti-LFA-1 mAb. Ly6C cross-linking; fluorescence microscopy of LFA-1 clustering; pharmacological inhibitors (cytochalasin, calpain inhibitor, PI3-kinase inhibitor); capillary flow-adhesion assay with blocking anti-LFA-1 mAb Journal of immunology Medium 12538687
2010 RFX1 represses CD11a expression in CD4+ T cells by recruiting DNMT1, HDAC1, and histone methyltransferase SUV39H1 to the CD11a and CD70 promoters, maintaining DNA methylation, histone deacetylation, and H3K9 trimethylation; RFX1 downregulation in SLE reduces these repressive marks and causes CD11a overexpression. RFX1 co-immunoprecipitates with SUV39H1, and overexpressing/knocking down RFX1 controls H3K9me3 and CD11a expression levels. ChIP for H3K9me3 at CD11a promoter; co-immunoprecipitation of RFX1 and SUV39H1; RFX1 overexpression and siRNA knockdown; Western blot and immunofluorescence; RT-PCR for CD11a mRNA; SLE patient vs. healthy control CD4+ T cells Journal of autoimmunity; Arthritis research & therapy High 20223637 21192791
2013 CD11a (ITGAL) is required for CD8+ T cell accumulation, activation, and proliferation in adipose tissue during obesity; CD11a-deficient obese mice showed dramatically reduced T cell infiltration, activation, and interferon-gamma expression in adipose tissue; adoptive transfer of CD11a-deficient CD8+ T cells failed to infiltrate adipose tissue of obese wild-type recipients, directly demonstrating a cell-intrinsic role for CD11a in T cell migration to adipose tissue. CD11a knockout mice; adoptive transfer of WT vs. CD11a-deficient CD8+ T cells; flow cytometry for T cell phenotype; in vitro stimulation with IL-12/IL-18; insulin resistance measurement Arteriosclerosis, thrombosis, and vascular biology High 24158516
2013 CD11a deficiency in mice reduces the magnitude of the primary CD8 T cell response to Listeria monocytogenes, decreases differentiation into short-lived effector cells (KLRG1hi CD127lo), and greatly enhances generation of CD62L+ central memory cells; CD11b or CD11c deficiency had no effect, establishing a specific non-redundant role for CD11a in effector differentiation. Secondary responses were robust despite CD11a deficiency. CD11a-, CD11b-, and CD11c-deficient mice infected with L. monocytogenes; flow cytometry for KLRG1, CD127, CD62L, cytokine and granzyme B production Infection and immunity High 23357382
2013 Natural genetic variation in Itgal (including coding SNPs, a 5-bp insertion in exon 30b, and altered expression of a splice variant) modulates ischemic brain infarct volume; mice lacking Itgal showed increased neuronal cell death in ex vivo brain slice and in vivo focal cerebral ischemia models, placing CD11a in a pathway controlling neuroprotection after ischemia. Quantitative trait locus mapping; reciprocal recombinant congenic mice; SNP haplotype analysis; CD11a knockout mice in ex vivo brain slice and in vivo focal ischemia models PLoS genetics High 24130503
2017 Histone demethylase JMJD3 regulates CD11a expression in lupus CD4+ T cells by removing H3K27me3 from the ITGAL promoter; SLE patients showed decreased H3K27me3 and increased JMJD3 binding at the ITGAL promoter; JMJD3 overexpression in healthy donor CD4+ T cells reduced H3K27me3 at the ITGAL promoter and upregulated CD11a expression; JMJD3 siRNA in SLE cells reversed these effects. ChIP for H3K27me3 and JMJD3 at ITGAL promoter; JMJD3 overexpression (pcDNA3.1-JMJD3 transfection); JMJD3 siRNA knockdown; RT-PCR for CD11a; SLE patient vs. healthy control T cells Oncotarget High 28430662
2019 LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) have distinct roles in neutrophil extravasation; using newly generated LFA-1 FRET (CD11a-YFP/CD18-CFP) and Mac-1 FRET mice with two-photon intravital imaging, LFA-1 was found to regulate neutrophil penetration through hotspot I (entry into the endothelial cell layer), while Mac-1 regulated transit through hotspot II (exit through basement membrane and pericyte sheath). Transgenic LFA-1 FRET (CD11a-YFP/CD18-CFP) and Mac-1 FRET mice; two-photon intravital imaging; transmission electron microscopy Experimental & molecular medicine High 30967528
2019 A loss-of-function variant in Itgal (ITGAL/CD11a) in CC042 mice increases susceptibility to Salmonella Typhimurium infection; the causative role was confirmed by quantitative complementation test, indicating CD11a contributes to host defense against systemic Salmonella in a genetic background-dependent manner. F2 cross QTL mapping; quantitative complementation test with CD11a loss-of-function variant; bacterial load quantification; immune cell phenotyping Infection and immunity High 31636138
2022 CD11a expressed on glioma-associated microglia (GAM) is required for CX3CR1 (Cx3cr1) expression, CX3CL1-directed microglia motility, and CCL5 (glioma mitogen) production; CD11a-knockout microglia showed reduced Cx3cr1 expression and impaired CX3CL1-directed migration. In vivo, antibody-mediated CD11a inhibition reduced Nf1 optic glioma growth in mice. CD11a-knockout mouse microglia in vitro functional studies; anti-CD11a neutralizing antibody treatment of Nf1 optic glioma mice in vivo; RNAScope and immunohistochemistry; RNA-seq meta-analysis Neuro-oncology High 34043012
2013 Spermine-mediated suppression of LFA-1 expression is mechanistically linked to enhanced DNA methylation of the ITGAL promoter; inhibition of ornithine decarboxylase (reducing polyamines) decreased DNMT activity and enhanced ITGAL demethylation, increasing CD11a expression; spermine supplementation restored DNMT activity, enhanced ITGAL methylation, and reduced CD11a expression. Spermine acts by modulating the methyl donor SAM through effects on S-adenosyl-L-methionine decarboxylase. DFMO-mediated polyamine depletion; extracellular spermine supplementation; DNMT activity measurement; bisulfite sequencing of ITGAL promoter; CD11a protein expression (flow cytometry); SAM/decarboxylated-SAM manipulation; Western blot for Rap1 PloS one Medium 23418509
2009 Genetic deficiency of ItgaL (CD11a) completely prevents autoimmune diabetes development in NOD/LtJ mice and prevents insulitis, but through a mechanism distinct from Itgb2 deficiency: ItgaL deficiency does not alter NOD T cell adhesion to or transmigration across islet endothelial cells; adoptive transfer of ItgaL-deficient splenocytes into NOD/Rag-1 mice failed to cause diabetes, indicating ItgaL is required for T cell activation rather than adhesion/trafficking in this context. Gene-targeted ItgaL-deficient NOD/LtJ mice; insulitis and diabetes incidence monitoring; in vitro hydrodynamic flow adhesion studies with islet microvascular endothelial cells; adoptive transfer into NOD/Rag-1 mice Diabetes High 19223596

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proceedings of the National Academy of Sciences of the United States of America 370 16380428
2002 Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus. Arthritis and rheumatism 222 12115234
1989 Two leukocyte receptors (CD11a/CD18 and CD11b/CD18) mediate transient adhesion to endothelium by binding to different ligands. Journal of immunology (Baltimore, Md. : 1950) 222 2809204
1991 CD40 signaling activates CD11a/CD18 (LFA-1)-mediated adhesion in B cells. Journal of immunology (Baltimore, Md. : 1950) 218 1706378
2001 Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1. Journal of immunology (Baltimore, Md. : 1950) 214 11544294
1999 Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. Journal of molecular biology 200 10493852
2002 Psoriasis as a model for T-cell-mediated disease: immunobiologic and clinical effects of treatment with multiple doses of efalizumab, an anti-CD11a antibody. Archives of dermatology 182 12020219
2000 Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis. Journal of the American Academy of Dermatology 166 10688712
1992 Antigen-receptor complex stimulation triggers protein kinase C-dependent CD11a/CD18-cytoskeleton association in T lymphocytes. The Journal of cell biology 143 1346786
1988 Triggering of co-mitogenic signals in T cell proliferation by anti-LFA-1 (CD18, CD11a), LFA-3, and CD7 monoclonal antibodies. Journal of immunology (Baltimore, Md. : 1950) 143 2459196
2010 Epigenetics and SLE: RFX1 downregulation causes CD11a and CD70 overexpression by altering epigenetic modifications in lupus CD4+ T cells. Journal of autoimmunity 135 20223637
1996 The role of the divalent cation in the structure of the I domain from the CD11a/CD18 integrin. Structure (London, England : 1993) 128 8805579
1993 Differential expression of cell adhesion molecules CD54/CD11a and CD58/CD2 by human melanoma cells and functional role in their interaction with cytotoxic cells. Cancer research 122 7686816
1992 Intercellular adhesion molecule-2, a second counter-receptor for CD11a/CD18 (leukocyte function-associated antigen-1), provides a costimulatory signal for T-cell receptor-initiated activation of human T cells. Journal of immunology (Baltimore, Md. : 1950) 121 1346150
2000 Sequential binding of CD11a/CD18 and CD11b/CD18 defines neutrophil capture and stable adhesion to intercellular adhesion molecule-1. Blood 109 10648403
1994 Role of CD11a and CD11b in ischemic acute renal failure in rats. The American journal of physiology 106 7810691
1999 Population pharmacokinetics and pharmacodynamics of the anti-CD11a antibody hu1124 in human subjects with psoriasis. Journal of pharmacokinetics and biopharmaceutics 103 10826130
1993 Monoclonal antibodies against ICAM-1 (CD54) and LFA-1 (CD11a/CD18) inhibit experimental autoimmune uveitis. Clinical immunology and immunopathology 96 8100190
1995 Both anti-CD11a (LFA-1) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis. Journal of neuroimmunology 92 7499503
2002 Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter. Mechanisms of ageing and development 88 12020947
1991 The role of CD11a/CD18-CD54 interactions in human T cell-dependent B cell activation. Journal of immunology (Baltimore, Md. : 1950) 88 1670945
1997 The neuronal glycoprotein telencephalin is a cellular ligand for the CD11a/CD18 leukocyte integrin. Journal of immunology (Baltimore, Md. : 1950) 86 8993013
2002 Bacterial fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14 and CD11a/CD18 as cellular receptors. European journal of immunology 78 12207338
2006 LFA-1 (CD11a) as a therapeutic target. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 74 16433753
2019 LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) distinctly regulate neutrophil extravasation through hotspots I and II. Experimental & molecular medicine 73 30967528
2018 The down-regulation of hsa_circ_0012919, the sponge for miR-125a-3p, contributes to DNA methylation of CD11a and CD70 in CD4+ T cells of systemic lupus erythematous. Clinical science (London, England : 1979) 73 30237316
1990 Participation of CD11a-c/CD18, CD2 and RGD-binding receptors in endogenous and interleukin-2-stimulated NK activity of CD3-negative large granular lymphocytes. International journal of cancer 73 1979068
1994 Role of polymorphonuclear neutrophil leukocytes and their integrin CD11a (LFA-1) in the pathogenesis of severe murine malaria. Infection and immunity 71 8132319
2010 RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the histone methyltransferase SUV39H1. Arthritis research & therapy 68 21192791
1990 Induction of cell-associated interleukin 1 through stimulation of the adhesion-promoting proteins LFA-1 (CD11a/CD18) and CR3 (CD11b/CD18) of human monocytes. European journal of immunology 65 1694134
2014 Hypomethylation and overexpression of ITGAL (CD11a) in CD4(+) T cells in systemic sclerosis. Clinical epigenetics 64 25414732
1998 Contribution of CD11a/CD18, CD11b/CD18, ICAM-1 (CD54) and -2 (CD102) to human monocyte migration through endothelium and connective tissue fibroblast barriers. European journal of immunology 64 9645379
1993 A peptide from ICAM-2 binds to the leukocyte integrin CD11a/CD18 and inhibits endothelial cell adhesion. The Journal of biological chemistry 61 8349630
1993 Effect of inhibitors of distinct signalling pathways on neutrophil Q2- generation in response to tumor necrosis factor-alpha, and antibodies against CD18 and CD11a: evidence for a common and unique pattern of sensitivity to wortmannin and protein tyrosine kinase inhibitors. Biochemical and biophysical research communications 60 8094958
1998 Cooperation between CD44 and LFA-1/CD11a adhesion receptors in lymphokine-activated killer cell cytotoxicity. Journal of immunology (Baltimore, Md. : 1950) 59 9637488
2013 Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue. Arteriosclerosis, thrombosis, and vascular biology 58 24158516
2002 Effect of DNA methylation and chromatin structure on ITGAL expression. Blood 55 12036881
1995 Adhesive glycoproteins CD11a and CD18 are upregulated in the leukocytes from patients with ischemic stroke and transient ischemic attacks. Journal of the neurological sciences 55 7722533
1993 Generation and characterization of monoclonal antibodies against rabbit CD4, CD5 and CD11a antigens. Journal of immunological methods 55 7678632
1991 Expression of the leucocyte integrin LFA-1 (CD11a/CD18) and its ligand ICAM-1 (CD54) in lymphoid malignancies is related to lineage derivation and stage of differentiation but not to tumor grade. Leukemia 54 1683677
2000 Binding of T lymphocytes to hippocampal neurons through ICAM-5 (telencephalin) and characterization of its interaction with the leukocyte integrin CD11a/CD18. European journal of immunology 52 10741396
2000 Effect of integrin beta 2 subunit truncations on LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) assembly, surface expression, and function. Journal of immunology (Baltimore, Md. : 1950) 52 10946284
1993 Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a gene. Proceedings of the National Academy of Sciences of the United States of America 51 8099450
2008 Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness. The Journal of investigative dermatology 50 18239614
1991 T lymphocyte adhesion to human synovial fibroblasts. Role of cytokines and the interaction between intercellular adhesion molecule 1 and CD11a/CD18. Arthritis and rheumatism 50 1681812
1996 CD11a-CD18 and CD102 interactions mediate human myeloma cell growth arrest induced by CD40 stimulation. Cancer research 48 8620513
1996 Total cell content of CR3 (CD11b/CD18) and LFA-1 (CD11a/CD18) in neonatal neutrophils: relationship to gestational age. Blood 46 8611722
2005 NK cell activity in tuberculosis is associated with impaired CD11a and ICAM-1 expression: a regulatory role of monocytes in NK activation. Immunology 43 16313368
1999 Blocking ICAM-1 (CD54) and LFA-1 (CD11a) inhibits experimental allergic conjunctivitis. Clinical immunology (Orlando, Fla.) 43 10527686
2018 CD11a expression distinguishes infiltrating myeloid cells from plaque-associated microglia in Alzheimer's disease. Glia 42 30588668
1996 Hyperoxia induces platelet activation and lung sequestration: an event dependent on tumor necrosis factor-alpha and CD11a. American journal of respiratory cell and molecular biology 41 8679214
2012 Moderate-intensity, premeal cycling blunts postprandial increases in monocyte cell surface CD18 and CD11a and endothelial microparticles following a high-fat meal in young adults. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 40 22519907
2003 Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2. Clinical and experimental immunology 40 12823280
2003 RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements. Blood 40 12855590
1993 Description of the leukocyte function-associated antigen 1 (LFA-1 or CD11a) promoter. Proceedings of the National Academy of Sciences of the United States of America 39 8097887
2003 Ly6C induces clustering of LFA-1 (CD11a/CD18) and is involved in subtype-specific adhesion of CD8 T cells. Journal of immunology (Baltimore, Md. : 1950) 38 12538687
1993 Characterization of the CD11a (alpha L, LFA-1 alpha) integrin gene promoter. The Journal of biological chemistry 38 8103515
1992 Induction of CD11a/leukocyte function antigen-1 and CD54/intercellular adhesion molecule-1 on hairy cell leukemia cells is accompanied by enhanced susceptibility to T-cell but not lymphokine-activated killer-cell cytotoxicity. Blood 37 1352710
2013 CD11a regulates effector CD8 T cell differentiation and central memory development in response to infection with Listeria monocytogenes. Infection and immunity 35 23357382
2002 Neutrophil migration into indomethacin induced rat small intestinal injury is CD11a/CD18 and CD11b/CD18 co-dependent. Gut 35 11950807
2000 Effects of humanized monoclonal antibody to rhesus CD11a in rhesus monkey cardiac allograft recipients. Transplantation 35 10852588
1993 A new CD43 monoclonal antibody induces homotypic aggregation of human leucocytes through a CD11a/CD18-dependent and -independent mechanism. Immunology 35 8099567
1992 Expression of the CD54 (ICAM-1) and CD11a (LFA-1) adhesion molecules in oral mucosal inflammation. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 35 1348286
2017 CD11a and CD49d enhance the detection of antigen-specific T cells following human vaccination. Vaccine 34 28662951
2002 The "ex vivo" patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR expression identify acute/early and chronic/late NK-cell activation states. Blood cells, molecules & diseases 33 12064914
1995 Identification of Sp1-binding sites in the CD11c (p150,95 alpha) and CD11a (LFA-1 alpha) integrin subunit promoters and their involvement in the tissue-specific expression of CD11c. European journal of immunology 33 8566043
2020 COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a+. Molecular therapy : the journal of the American Society of Gene Therapy 31 33186542
2003 Immune cell CD62L and CD11a expression in response to a psychological stressor in human hypertension. Brain, behavior, and immunity 31 12831828
2002 Lck tyrosine kinase is important for activation of the CD11a/CD18-integrins in human T lymphocytes. European journal of immunology 31 12115650
1993 Quantitative analysis of lymphocyte CD11a using standardized flow cytometry. Scandinavian journal of immunology 31 7902997
1989 Requirement of leukocytic cell adhesion molecules (CD11a-c/CD18) in the enhanced NK lysis of iC3b-opsonized targets. Journal of immunology (Baltimore, Md. : 1950) 31 2565929
1999 CD11a expression and soluble ICAM-1 levels in peripheral blood in high-risk and overt type 1 diabetes subjects. Immunology letters 30 10541054
2005 Tissue distribution and receptor-mediated clearance of anti-CD11a antibody in mice. Drug metabolism and disposition: the biological fate of chemicals 29 15673599
1996 Engagement of adhesion molecules (CD18, CD11a, CD45, CD44, and CD58) enhances human immunodeficiency virus type 1 replication in monocytic cells through a tumor necrosis factor-modulated pathway. The Journal of infectious diseases 28 8656013
1992 Regulation of expression of the leukocyte integrin CD11a (LFA-1) molecule during differentiation of HL-60 cells along the monocyte/macrophage pathway. Journal of immunology (Baltimore, Md. : 1950) 28 1730867
2022 RNA sequence analysis reveals ITGAL/CD11A as a stromal regulator of murine low-grade glioma growth. Neuro-oncology 27 34043012
1998 CD45RA(bright)/CD11a(bright) CD8+ T cells: effector T cells. International immunology 27 9885904
2019 Transcriptome profiling of brain myeloid cells revealed activation of Itgal, Trem1, and Spp1 in western diet-induced obesity. Journal of neuroinflammation 26 31426806
2017 Histone demethylase JMJD3 regulates CD11a expression through changes in histone H3K27 tri-methylation levels in CD4+ T cells of patients with systemic lupus erythematosus. Oncotarget 26 28430662
2004 Increased expression of monocyte CD11a and intracellular adhesion molecule-1 in patients with initial atherosclerotic coronary stenosis. Circulation journal : official journal of the Japanese Circulation Society 26 14695458
1999 Critical role of CD11a (LFA-1) in therapeutic efficacy of systemically transferred antitumor effector T cells. Cellular immunology 25 10087180
1996 Selective induction of CD11a,b,c/CD18 and CD54 expression at the cell surface of human leukocytes by muramyl peptides. Cellular immunology 25 8620558
2013 Natural genetic variation of integrin alpha L (Itgal) modulates ischemic brain injury in stroke. PLoS genetics 24 24130503
2000 Polyomavirus enhancer-binding protein 2/core binding factor/acute myeloid leukemia factors contribute to the cell type-specific activity of the CD11a integrin gene promoter. The Journal of biological chemistry 24 10882733
1992 Induction of homotypic T cell adhesion by triggering of leukocyte function-associated antigen-1 alpha (CD11a): differential effects on resting and activated T cells. European journal of immunology 24 1352499
2001 Porins from Salmonella enterica serovar Typhimurium induce TNF-alpha, IL-6 and IL-8 release by CD14-independent and CD11a/CD18-dependent mechanisms. Microbiology (Reading, England) 23 11577149
1994 Polymorphonuclear granulocyte expression of CD11a/CD18, CD11b/CD18 and L-selectin in normal individuals. FEMS immunology and medical microbiology 23 7516231
1999 Neutrophil inhibitory factor abrogates neutrophil adhesion by blockade of CD11a and CD11b beta(2) integrins. Molecular pharmacology 22 10531396
1991 Functional epitope analysis of the human CD11a/CD18 molecule (LFA-1, lymphocyte function-associated antigen 1) involved in HIV-1-induced syncytium formation. Scandinavian journal of immunology 22 1718027
2019 A Loss-of-Function Mutation in the Integrin Alpha L (Itgal) Gene Contributes to Susceptibility to Salmonella enterica Serovar Typhimurium Infection in Collaborative Cross Strain CC042. Infection and immunity 21 31636138
2003 Small molecule LFA-1 antagonists compete with an anti-LFA-1 monoclonal antibody for binding to the CD11a I domain: development of a flow-cytometry-based receptor occupancy assay. Journal of immunological methods 21 12799043
2009 Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ mice. Diabetes 20 19223596
2008 Selective CD11a upregulation on neutrophils in the acute phase of steroid-responsive meningitis-arteritis in dogs. Veterinary immunology and immunopathology 20 18760844
1993 CD11a/CD18 (LFA-1) integrin engagement enhances biosynthesis of early cytokines by activated T cells. Cellular immunology 20 8098668
2013 Suppression of LFA-1 expression by spermine is associated with enhanced methylation of ITGAL, the LFA-1 promoter area. PloS one 19 23418509
2010 VEGF₁₆₄ differentially regulates neutrophil and T cell adhesion through ItgaL- and ItgaM-dependent mechanisms. American journal of physiology. Gastrointestinal and liver physiology 19 20884890
2005 RUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters. Immunobiology 19 16164020
2025 Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells. Journal of nanobiotechnology 18 39885580
2017 CD4+CD28+KIR+CD11ahi T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients. Journal of autoimmunity 18 29066026
2012 Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL. Journal of lipid research 18 23160181

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