Affinage

LTA

Lymphotoxin-alpha · UniProt P01374

Length
205 aa
Mass
22.3 kDa
Annotated
2026-06-10
100 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Lymphotoxin-alpha (LTA) is a TNF-superfamily cytokine that operates in two functionally distinct forms to drive proinflammatory endothelial activation and to organize peripheral lymphoid tissue (PMID:1969453, PMID:9862717, PMID:12732657). As a secreted homotrimer (LTα3), it engages a shared ~80 kDa TNF receptor on T lymphocytes as a partial agonist with 10- to 20-fold lower affinity than TNF, inducing MHC class I (PMID:1969453), and on endothelium drives adhesion molecules (VCAM-1, ICAM-1, E-selectin, MAdCAM-1) and chemokines (RANTES, IP-10, MCP-1) while also mediating target-cell cytotoxicity (PMID:9862717); LTα additionally binds a site on the HVEM (HveA) receptor distinct from those used by LIGHT and herpes glycoprotein D (PMID:11164894). When co-expressed with LT-beta, the membrane-anchored LTαβ heteromer signals through LTβR (via TRAF-2/3/5 adaptors) to govern lymphoid architecture: LTαβ-LTβR signaling, but not LTα3 alone, drives HEC-6ST-dependent luminal PNAd on high endothelial venules and full T/B compartmentalization and FDC networks (PMID:12732657), positions mature dendritic cells in the spleen (PMID:12560241), maintains fibroblastic reticular cell structure and CCL21/CCL19 output (PMID:25266629), and during Listeria infection directs intestinal goblet cell differentiation and MUC2 production through alternative (RelB) NF-κB in epithelial cells (PMID:32591396). LTα expression is itself tightly controlled, regulated both transcriptionally and by mRNA stabilization upon TCR engagement and held in check by a labile repressor (PMID:8157957); the TNFB*2 polymorphism is associated with reduced LTα protein output from stimulated PBMCs and enriched in lupus nephritis (PMID:9302664).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1990 High

    Established that LTα and TNF act through a common cell-surface receptor, defining LTα as a lower-affinity partial agonist rather than a ligand with an entirely separate receptor system.

    Evidence Radioligand binding, competitive displacement, and chemical cross-linking with MHC class I induction on human T cells

    PMID:1969453

    Open questions at the time
    • Did not distinguish TNFR1 vs TNFR2 contributions
    • Did not address the membrane LTαβ heteromer or LTβR
  2. 1994 Medium

    Showed LTα is rate-limiting for membrane LTαβ heteromer formation and is controlled by both transcription and mRNA stabilization downstream of TCR signaling, explaining how activated T cells tune lymphotoxin output.

    Evidence Nuclear run-on, mRNA decay, and cycloheximide superinduction in murine T cell clones

    PMID:8157957

    Open questions at the time
    • Identity of the labile repressor of LT mRNA unknown
    • Mechanism stabilizing LT mRNA not defined
  3. 1998 Medium

    Defined the proinflammatory program of secreted LTα3 independent of LT-beta, linking it to endothelial adhesion molecule and chemokine induction and direct cytotoxicity.

    Evidence Cytotoxicity, ELISA, Northern blot, and immunofluorescence on a murine endothelial line with cross-species ligand comparison

    PMID:9862717

    Open questions at the time
    • Receptor (TNFR1/2) mediating each endothelial readout not resolved
    • Did not show LTα3 fails to induce PNAd via LTβR
  4. 2000 Medium

    Mapped LTα to a distinct epitope on HVEM separate from LIGHT and viral gD binding sites, revealing receptor-level ligand competition and conformational coupling.

    Evidence Competitive binding with truncated receptor ectodomains, monoclonal antibodies, and peptide ligands

    PMID:11164894

    Open questions at the time
    • Functional consequence of LTα-HVEM engagement not established
    • Affinities and cellular context not defined
  5. 2003 High

    Separated the architectural roles of the two LTα forms, demonstrating that LTαβ heteromer—not LTα3—drives HEC-6ST-dependent luminal PNAd and complete lymphoid compartmentalization.

    Evidence Comparison of RIPLTα, RIPLTαβ, and LTβ-/- transgenic/knockout mice with IHC and in situ hybridization

    PMID:12732657

    Open questions at the time
    • Did not define upstream signaling linking LTβR to HEC-6ST transcription
    • Ectopic model may not fully reflect physiologic HEV development
  6. 2003 High

    Distinguished TNF-dependent DC development from LTα/LTβ-LTβR-dependent peripheral DC positioning, assigning LTα a non-redundant role in splenic DC retention.

    Evidence Single and triple knockout mice, bone marrow culture reconstitution with rTNF, and antibody blocking

    PMID:12560241

    Open questions at the time
    • Microenvironmental chemokines mediating DC retention not pinned down in this study
    • Did not separate LTα3 vs LTαβ contributions to positioning
  7. 2007 Low

    Assigned TRAF-2/3/5 as the adaptors coupling LTβR to transcription and cell death while noting that TRAF-deficient mice do not phenocopy LTβR loss, implying additional pathway components.

    Evidence Synthesis of TRAF-deficient and LTβR-deficient mouse genetics (review)

    PMID:17633025

    Open questions at the time
    • Review without new primary data
    • Compensatory/additional adaptors unidentified
  8. 2007 Medium

    Demonstrated that LTαβ-LTβR signaling promotes demyelination and that its blockade accelerates remyelination, extending LTα function to CNS glial pathology.

    Evidence LTβR-/- mice plus LTβR-Ig decoy treatment in the cuprizone demyelination model with myelin staining

    PMID:17626203

    Open questions at the time
    • Cellular source of LT acting on glia not defined
    • Downstream microglial/astroglial effectors unresolved
  9. 2007 Low

    Implicated LTαβ-LTβR signaling in thymic ontogeny of unconventional T cells (γδ, iNKT) and in central tolerance.

    Evidence Synthesis of LTβR-deficient thymic development phenotypes (review)

    PMID:17336158

    Open questions at the time
    • Review without new primary data
    • Stromal vs thymocyte LTβR contributions not dissected here
  10. 2014 Medium

    Established that T-cell-derived lymphotoxin maintains splenic fibroblastic reticular cell structure and chemokine output through its receptor.

    Evidence Nude mouse T-cell depletion, T-cell transfusion reconstitution, and LTβR blockade with IHC and qRT-PCR

    PMID:25266629

    Open questions at the time
    • Did not formally separate LTα3 from LTαβ contributions to FRC maintenance
    • Single-lab reconstitution model
  11. 2015 Low

    Framed LTβR as activating both classical and non-classical NF-κB and inducing apoptosis despite lacking a death domain, distinguishing it from canonical death receptors.

    Evidence Review and synthesis of TNFR-family signaling experiments

    PMID:26028499

    Open questions at the time
    • Review without new primary data
    • Molecular basis of death-domain-independent killing not specified
  12. 2020 High

    Showed ILC3-derived lymphotoxin acts on epithelial LTβR to drive goblet cell differentiation and MUC2 via RelB during infection, linking LTα to mucosal host defense through alternative NF-κB.

    Evidence ILC3-specific LT and IEC-specific LTβR conditional knockouts, single KO mice, RelB pathway analysis, and Listeria challenge

    PMID:32591396

    Open questions at the time
    • Whether epithelial effect requires LTαβ vs LTα3 not isolated
    • RelB target genes driving goblet differentiation not enumerated
  13. 1997 Medium

    Linked the TNFB*2 polymorphism to reduced LTα protein production from stimulated PBMCs and to lupus nephritis, giving a functional readout of an LTA genetic variant.

    Evidence PHA stimulation of PBMCs with ELISA and bioassay plus PCR-NcoI RFLP genotyping in an SLE cohort

    PMID:9302664

    Open questions at the time
    • Mechanism by which TNFB*2 lowers LTα expression not defined
    • Association does not establish causation in lupus nephritis

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the choice between secreted LTα3 (TNFR/HVEM) and membrane LTαβ (LTβR) signaling is regulated in vivo, and which downstream effectors translate LTβR-RelB activation into tissue-specific architectural programs, remains unresolved.
  • No structural model of LTα-receptor complexes in the corpus
  • Quantitative control of LTα3 vs LTαβ partitioning unknown
  • Direct RelB target genes for each tissue program not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5
Localization
GO:0005576 extracellular region 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
LTBLTBRTNFRSF14TNFRSF1ATRAF2TRAF3TRAF5

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 LT (lymphotoxin-alpha) and TNF bind to a common cell surface receptor of approximately 80 kDa on human T lymphocytes, but LT is 10- to 20-fold less effective than TNF in competitive displacement of radiolabeled TNF. Cross-linking experiments revealed distinct adduct sizes (92 kDa for TNF, 104 kDa for LT), yet rTNF inhibited formation of the LT adduct, confirming a shared receptor. LT functioned as a partial agonist relative to TNF in inducing MHC class I expression, consistent with its lower receptor binding affinity. Radioligand binding assays (direct and competitive), chemical cross-linking with SDS-PAGE autoradiography, MHC class I induction assay on human T cell hybridoma Journal of immunology High 1969453
1994 In murine T cell clones activated through the TCR via anti-CD3, LT (lymphotoxin-alpha) mRNA accumulation is regulated both transcriptionally and post-transcriptionally: anti-CD3 substantially increases LT gene transcription and also stabilizes LT mRNA (half-life 3-4 times longer than TNF-alpha mRNA). Cycloheximide superinduces LT mRNA post-transcriptionally but not TNF-alpha or LT-beta mRNA, indicating a labile repressor specifically restrains LT mRNA. LT production appears to be rate-limiting for formation of the membrane LT-alpha/LT-beta heteromeric complex. Nuclear run-on transcription assay, mRNA stability assay, cycloheximide superinduction, Northern blot, RT-PCR in murine T cell clones Journal of immunology Medium 8157957
1998 Recombinant murine LTalpha3 (the homotrimeric secreted form) induces expression of adhesion molecules VCAM-1, ICAM-1, E-selectin, and MAdCAM-1 on murine endothelial cells (bEnd.3 line), and induces chemokines RANTES, IP-10, and MCP-1. mLTalpha was more potent than human LTalpha or mTNF-alpha in inducing MAdCAM-1. None of these cytokines induced PNAd. mLTalpha also mediated cytotoxicity of WEHI target cells (ED50 ~1.2 ng/ml). These proinflammatory activities are distinct from those requiring LT-beta co-expression. Cytotoxicity assay, ELISA, Northern blot, immunofluorescence on murine endothelial cell line; comparison with human LTalpha and mTNF-alpha Journal of immunology Medium 9862717
2000 LT-alpha (lymphotoxin-alpha) and LIGHT bind to distinct sites on the herpes virus entry mediator A (HveA/HVEM) receptor, separate from the herpes simplex virus glycoprotein gD binding site. Two HveA peptide ligands (BP-1 and BP-2) differentially inhibited binding of soluble gD versus LT-alpha to the receptor, and competitive binding experiments with monoclonal antibodies and truncated receptor ectodomains (full-length HveA(200t) vs. two N-terminal CRP domains HveA(120t)) demonstrated that gD, LIGHT, and LT-alpha each engage distinct receptor epitopes. Binding of one ligand to HveA may alter receptor conformation and affect interaction with other ligands. Competitive binding assays with recombinant receptor ectodomains, monoclonal antibody inhibition, synthetic peptide ligand competition Molecular immunology Medium 11164894
2003 In a mouse model of ectopic lymphoid organogenesis, simultaneous expression of both LT-alpha and LT-beta (under RIP control) produced qualitatively distinct pancreatic infiltrates compared to LT-alpha alone: more complete T/B cell compartmentalization, prominent FDC networks, more intense lymphoid chemokines (CCL21, CCL19, CXCL13), and more frequent L-selectin+ cells. Crucially, luminal PNAd expression (dependent on the HEV-restricted sulfotransferase HEC-6ST) required LTalphabeta signaling, whereas LT-alpha alone drove only abluminal PNAd, similar to LTbeta-/- MLN. This establishes that LTalphabeta heteromer (membrane-bound form) drives HEC-6ST-dependent luminal PNAd in a manner distinct from homotrimeric LTalpha3. Transgenic mouse comparison (RIPLTalpha vs. RIPLTalphabeta vs. LTbeta-/- mice), immunohistochemistry, in situ hybridization for chemokines and addressins The Journal of experimental medicine High 12732657
2003 In TNF/LTalpha/LTbeta triple-knockout mice, DC numbers in spleen are significantly reduced. Bone marrow culture experiments dissected individual contributions: TNF acting through TNFR p55 is required for DC development/maturation from bone marrow progenitors (reversible by exogenous rTNF), whereas LTalpha/LTbeta signaling through LTbetaR is specifically required for recruitment/retention of mature DCs in peripheral lymphoid organs (spleen). LTalpha-/-, LTbeta-/-, and LTbetaR-/- mice had normal BM DC production but reduced splenic DCs, confirming a non-redundant role for LTalpha in peripheral DC positioning via LTbetaR-dependent microenvironmental chemokine production. Bone marrow culture with GM-CSF/IL-4, flow cytometry, single and triple knockout mouse analysis, antibody blocking experiments Blood High 12560241
2007 The LTbeta receptor (LTbetaR) signaling pathway operates through TNFR-associated factors (TRAF)-2, -3, and -5 as adaptors linking receptor activation to downstream gene transcription and cell death. However, TRAF-deficient mice do not phenocopy LTbetaR-deficient mice, indicating that TRAFs are necessary but that additional or compensatory mechanisms exist in the LTbetaR pathway. Genetic analysis of TRAF-deficient and LTbetaR-deficient mouse phenotypes (review/synthesis of prior experiments) Advances in experimental medicine and biology Low 17633025
2007 In the cuprizone model of demyelination, LTbetaR is upregulated during the demyelination phase in areas enriched with microglia and astroglia. LTbetaR gene deletion (LTbetaR-/-) significantly delayed demyelination but also slightly delayed remyelination. An LTbetaR-Ig decoy fusion protein (blocking LTalphabeta-LTbetaR signaling) delayed demyelination in wild-type mice and dramatically accelerated remyelination even after maximal disease, demonstrating that LTalphabeta-LTbetaR signaling promotes demyelination via microglial/astroglial pathways and that its blockade benefits remyelination. LTbetaR-/- mouse analysis, LTbetaR-Ig decoy protein treatment, cuprizone demyelination model, immunohistochemistry for LTbetaR, myelin staining The Journal of neuroscience Medium 17626203
2007 The LTalphabeta-LTbetaR pathway has a pivotal role in the ontogeny of unconventional T cells, including gammadelta T cells and invariant NKT cells, operating at multiple levels during thymic development. Double-positive thymocytes regulate differentiation of early thymocyte progenitors and gammadelta T cells through a mechanism dependent on LTbetaR. LTbetaR signaling in thymic stroma also affects central tolerance to peripherally restricted antigens. Analysis of LTbetaR-deficient mouse thymic development, flow cytometry of T cell subsets (review of accumulated evidence) Trends in immunology Low 17336158
2014 T lymphocytes maintain the structure and function of splenic fibroblastic reticular cells (FRCs) via lymphotoxin-B (LT-B). In nude mice lacking T cells, FRCs showed structural disorder, downregulated CCL21 and CCL19 chemokines, and reduced ER-TR7 secretion. Transfusion of T cells restored FRC structure and function, but this restoration was abolished by blocking the LT-B receptor, establishing that T-cell-derived LT-B acting through its receptor is required for FRC homeostasis. Nude mouse model (T cell-deficient), T cell transfusion reconstitution, LTbetaR blockade, immunohistochemistry, flow cytometry, qRT-PCR for CCL21/CCL19 BMC immunology Medium 25266629
2015 Lymphotoxin (LT) receptor signaling activates both classical and non-classical NF-κB pathways and can induce apoptosis in non-lymphoid cells. The LTbetaR lacks a classical death domain yet can trigger cell death, and exhibits cell-type- and context-specific signaling that differs from canonical death receptors (TNFRI, Fas, TRAIL-R) and is functionally distinct from CD40 signaling within the TNF superfamily. Review and synthesis of published signaling experiments; comparison of intracellular signaling pathways across TNFR family members Cytokine & growth factor reviews Low 26028499
2020 Type 3 innate lymphoid cells (ILC3s) direct goblet cell differentiation and MUC2 production during Listeria infection through ILC3-derived lymphotoxin (LT) acting on LTbetaR expressed on intestinal epithelial cells (IECs). Conditional knockout of LT in ILC3s, or IEC-specific deletion of LTbetaR, impaired goblet cell differentiation-related gene expression and MUC2 production without affecting IEC proliferation or cell death. The alternative NF-κB pathway (RelB) in IECs downstream of LTbetaR was required for goblet cell differentiation gene expression and anti-Listeria defense. Villin-Cre conditional LTbetaR knockout, ILC3-specific LT conditional knockout, single gene-deficient (LT-/-, LIGHT-/- ) mice, Ki-67/Annexin V staining, RelB pathway analysis, Listeria challenge model Journal of immunology High 32591396
1997 SLE patients homozygous for TNFB*2 produce significantly less TNF-beta (lymphotoxin-alpha) protein than TNFB*1 homozygotes when peripheral blood mononuclear cells are stimulated with PHA (mean: 642 vs. 1126 pg/ml by ELISA, P=0.021). This reduced LT-alpha production associated with TNFB*2 homozygosity was significantly more frequent in lupus nephritis patients, suggesting a functional consequence of the TNFB polymorphism on protein expression levels. PHA stimulation of PBMCs, ELISA for TNF-beta protein, bioassay for TNF, TNFB genotyping by PCR-NcoI RFLP Lupus Medium 9302664

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. The Journal of biological chemistry 478 12594207
1991 NIT-1, a pancreatic beta-cell line established from a transgenic NOD/Lt mouse. Diabetes 243 1647994
1998 Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene. Vaccine 217 9682399
2003 Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase. The Journal of experimental medicine 206 12732657
2003 Pneumococcal lipoteichoic acid (LTA) is not as potent as staphylococcal LTA in stimulating Toll-like receptor 2. Infection and immunity 143 14500472
2007 A Staphylococcus aureus ypfP mutant with strongly reduced lipoteichoic acid (LTA) content: LTA governs bacterial surface properties and autolysin activity. Molecular microbiology 120 17640274
1992 Intrathymic islet cell transplantation reduces beta-cell autoimmunity and prevents diabetes in NOD/Lt mice. Diabetes 112 1446808
2010 Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium. American journal of epidemiology 109 20047977
1998 Lymphotoxin alpha3 induces chemokines and adhesion molecules: insight into the role of LT alpha in inflammation and lymphoid organ development. Journal of immunology (Baltimore, Md. : 1950) 98 9862717
2015 Folate Receptor-Positive Circulating Tumor Cell Detected by LT-PCR-Based Method as a Diagnostic Biomarker for Non-Small-Cell Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 97 26200270
2016 Ectopic expression of CXCL13, BAFF, APRIL and LT-β is associated with artery tertiary lymphoid organs in giant cell arteritis. Annals of the rheumatic diseases 76 27098405
2008 Association between LTA, TNF and AGER polymorphisms and late diabetic complications. PloS one 76 18575614
2017 Extracellular Hsp70 induces inflammation and modulates LPS/LTA-stimulated inflammatory response in THP-1 cells. Cell stress & chaperones 68 29067554
2006 LTA and LPS mediated activation of protein kinases in the regulation of inflammatory cytokines expression in macrophages. Clinica chimica acta; international journal of clinical chemistry 68 16899235
1993 Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus: TNFB-MHC haplotypes. Immunogenetics 67 8436420
1997 Retardation or acceleration of diabetes in NOD/Lt mice mediated by intrathymic administration of candidate beta-cell antigens. Diabetes 63 9392483
2009 TNF and LTA gene, allele, and extended HLA haplotype associations with severe dengue virus infection in ethnic Thais. The Journal of infectious diseases 62 19392621
2014 Differential localization of LTA synthesis proteins and their interaction with the cell division machinery in Staphylococcus aureus. Molecular microbiology 59 24533796
1990 Characterization of the receptor for tumor necrosis factor (TNF) and lymphotoxin (LT) on human T lymphocytes. TNF and LT differ in their receptor binding properties and the induction of MHC class I proteins on a human CD4+ T cell hybridoma. Journal of immunology (Baltimore, Md. : 1950) 59 1969453
1992 Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice. The Journal of clinical investigation 58 1361492
2003 Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo. Blood 56 12560241
2022 <b>The control of carpel determinacy pathway leads to sex determination</b> <b>in cucurbits</b> Science (New York, N.Y.) 55 36378960
1991 Haplotypic polymorphisms of the TNFB gene. Immunogenetics 52 1671667
2006 Lipoteichoic acid (LTA) from Staphylococcus aureus stimulates human neutrophil cytokine release by a CD14-dependent, Toll-like-receptor-independent mechanism: Autocrine role of tumor necrosis factor-[alpha] in mediating LTA-induced interleukin-8 generation. Critical care medicine 50 16521278
2006 Bruton's tyrosine kinase together with PI 3-kinase are part of Toll-like receptor 2 multiprotein complex and mediate LTA induced Toll-like receptor 2 responses in macrophages. Cellular signalling 50 17020802
2001 TNF and LTA gene polymorphisms reveal different risk in gastric and duodenal ulcer patients. Genes and immunity 49 11781708
2013 Antimicrobial peptide LL-37 attenuates LTA induced inflammatory effect in macrophages. International immunopharmacology 48 23375934
1994 Differential regulation of lymphotoxin (LT), lymphotoxin-beta (LT-beta), and TNF-alpha in murine T cell clones activated through the TCR. Journal of immunology (Baltimore, Md. : 1950) 48 8157957
1988 Structure and expression of the ompB operon, the regulatory locus for the outer membrane porin regulon in Salmonella typhimurium LT-2. Journal of molecular biology 48 2845093
2012 SNPs in PTGS2 and LTA predict pain and quality of life in long term lung cancer survivors. Lung cancer (Amsterdam, Netherlands) 46 22464751
2000 Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins LT-IIa and LT-IIb. Infection and immunity 46 10603399
2014 LPS- and LTA-induced expression of IL-6 and TNF-α in neonatal and adult blood: role of MAPKs and NF-κB. Mediators of inflammation 45 25530682
1987 Ovulation and fertilization of primary and secondary oocytes in LT/Sv strain mice. Gamete research 45 3507361
2019 Bacillus pumilus SE5 originated PG and LTA tuned the intestinal TLRs/MyD88 signaling and microbiota in grouper (Epinephelus coioides). Fish & shellfish immunology 41 30849499
2007 Lymphotoxin beta receptor (Lt betaR): dual roles in demyelination and remyelination and successful therapeutic intervention using Lt betaR-Ig protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 17626203
1996 Systemic lupus erythematosus with nephritis is strongly associated with the TNFB*2 homozygote in the Korean population. Human immunology 39 9157084
2015 Performances and Reliability of Bruker Microflex LT and VITEK MS MALDI-TOF Mass Spectrometry Systems for the Identification of Clinical Microorganisms. BioMed research international 37 26793718
2005 Mucosal adjuvant properties of mutant LT-IIa and LT-IIb enterotoxins that exhibit altered ganglioside-binding activities. Infection and immunity 37 15731030
2012 Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case-control study. BMC infectious diseases 36 23148654
2007 Selective use of TRAM in lipopolysaccharide (LPS) and lipoteichoic acid (LTA) induced NF-kappaB activation and cytokine production in primary human cells: TRAM is an adaptor for LPS and LTA signaling. Journal of immunology (Baltimore, Md. : 1950) 36 17277119
2000 The three HveA receptor ligands, gD, LT-alpha and LIGHT bind to distinct sites on HveA. Molecular immunology 36 11164894
2004 Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans. Genes and immunity 33 15306845
2020 PGN and LTA from Staphylococcus aureus Induced Inflammation and Decreased Lactation through Regulating DNA Methylation and Histone H3 Acetylation in Bovine Mammary Epithelial Cells. Toxins 32 32283626
1999 TNFA and TNFB polymorphisms in myasthenia gravis. Archives of neurology 32 10199335
2024 Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease. Nature communications 31 38238335
2014 Lipoteichoic acid (LTA) and lipopolysaccharides (LPS) from periodontal pathogenic bacteria facilitate oncogenic herpesvirus infection within primary oral cells. PloS one 31 24971655
2013 Tumor necrosis factor B (TNFB) genetic variants and its increased expression are associated with vitiligo susceptibility. PloS one 31 24312346
2010 Extended LTA, TNF, LST1 and HLA gene haplotypes and their association with rubella vaccine-induced immunity. PloS one 31 20668555
2009 Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine. Journal of neurology 31 20035431
2007 The A subunit of type IIb enterotoxin (LT-IIb) suppresses the proinflammatory potential of the B subunit and its ability to recruit and interact with TLR2. Journal of immunology (Baltimore, Md. : 1950) 31 17404262
2009 TNF, LTA, HSPA1L and HLA-DR gene polymorphisms in HIV-positive patients with hypersensitivity to cotrimoxazole. Pharmacogenomics 30 19374512
2007 The LT beta R signaling pathway. Advances in experimental medicine and biology 28 17633025
1997 TNFB polymorphisms characterize three lineages of TNF region microsatellite haplotypes. Immunogenetics 28 9382915
2020 6-Gingerol exerts anti-inflammatory effects and protective properties on LTA-induced mastitis. Phytomedicine : international journal of phytotherapy and phytopharmacology 27 32531697
2019 20-Hydroxy- and 20-carboxy-leukotriene (LT) B4 downregulate LTB4 -mediated responses of human neutrophils and eosinophils. Journal of leukocyte biology 27 30676680
2016 Synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy. Bioorganic & medicinal chemistry 27 28065501
2002 TNF alpha and LT alpha gene polymorphisms as additional markers of celiac disease susceptibility in a DQ2-positive population. Immunogenetics 27 12439617
2017 The development of novel LTA4H modulators to selectively target LTB4 generation. Scientific reports 26 28303931
2015 Modelling MS: Chronic-Relapsing EAE in the NOD/Lt Mouse Strain. Current topics in behavioral neurosciences 26 26126592
2003 Expression of lymphotoxin-beta (LT-beta) in chronic inflammatory conditions. The Journal of pathology 26 12474234
2019 NLRC5 negatively regulates LTA-induced inflammation via TLR2/NF-κB and participates in TLR2-mediated allergic airway inflammation. Journal of cellular physiology 25 30945291
2019 Characterization of the first insect prostaglandin (PGE2) receptor: MansePGE2R is expressed in oenocytoids and lipoteichoic acid (LTA) increases transcript expression. Insect biochemistry and molecular biology 25 31790798
2018 Induction of IL-10-balanced immune profiles following exposure to LTA from Staphylococcus epidermidis. Experimental dermatology 25 29569765
2002 Major histocompatibility complex class I chain related (MIC) A gene, TNFa microsatellite alleles and TNFB alleles in juvenile idiopathic arthritis patients from Latvia. Human immunology 25 11975986
2020 The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells. Toxins 24 32545333
2019 Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt. eLife 24 31194677
2018 Significance of Enterotoxigenic Escherichia coli (ETEC) Heat-Labile Toxin (LT) Enzymatic Subunit Epitopes in LT Enterotoxicity and Immunogenicity. Applied and environmental microbiology 24 29802193
2000 Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients. Journal of investigational allergology & clinical immunology 24 10923589
2017 Capturing LTA4 hydrolase in action: Insights to the chemistry and dynamics of chemotactic LTB4 synthesis. Proceedings of the National Academy of Sciences of the United States of America 23 28827365
2013 Genetic variations in CTLA-4, TNF-α, and LTA and susceptibility to T-cell lymphoma in a Chinese population. Cancer epidemiology 22 24035239
2021 LT-171-861, a novel FLT3 inhibitor, shows excellent preclinical efficacy for the treatment of FLT3 mutant acute myeloid leukemia. Theranostics 21 33391463
2019 MyD88 hypermethylation mediated by DNMT1 is associated with LTA-induced inflammatory response in human odontoblast-like cells. Cell and tissue research 21 30707290
2009 Mammalian cell ganglioside-binding specificities of E. coli enterotoxins LT-IIb and variant LT-IIb(T13I). Glycobiology 21 19749203
1997 Decreased tumour necrosis factor-beta production in TNFB*2 homozygote: an important predisposing factor of lupus nephritis in Koreans. Lupus 21 9302664
2023 Anti-inflammatory effects of chlorogenic acid from Taraxacum officinale on LTA-stimulated bovine mammary epithelial cells via the TLR2/NF-κB pathway. PloS one 20 36947494
2020 GtcA is required for LTA glycosylation in Listeria monocytogenes serovar 1/2a and Bacillus subtilis. Cell surface (Amsterdam, Netherlands) 20 32743150
2015 Association between ANKK1 (rs1800497) and LTA (rs909253) Genetic Variants and Risk of Schizophrenia. BioMed research international 20 26114114
2012 Increased expression of PcG protein YY1 negatively regulates B cell development while allowing accumulation of myeloid cells and LT-HSC cells. PloS one 20 22292011
2014 T lymphocytes maintain structure and function of fibroblastic reticular cells via lymphotoxin (LT)-B. BMC immunology 18 25266629
2011 Frequency and large T (LT) sequence of JC polyomavirus DNA in oligodendrocytes, astrocytes and granular cells in non-PML brain. Brain pathology (Zurich, Switzerland) 18 21951346
2010 Diabetic retinopathy: Validation study of ALR2, RAGE, iNOS and TNFB gene variants in a south Indian cohort. Ophthalmic genetics 18 21067489
2007 The unconventional role of LT alpha beta in T cell differentiation. Trends in immunology 18 17336158
2024 Processing of LtaS restricts LTA assembly and YSIRK preprotein trafficking into Staphylococcus aureus cross-walls. mBio 17 38174934
2020 Type 3 Innate Lymphoid Cells Direct Goblet Cell Differentiation via the LT-LTβR Pathway during Listeria Infection. Journal of immunology (Baltimore, Md. : 1950) 17 32591396
2020 HEMA-induced oxidative stress inhibits NF-κB nuclear translocation and TNF release from LTA- and LPS-stimulated immunocompetent cells. Dental materials : official publication of the Academy of Dental Materials 17 33303231
2019 Evaluation of the reactogenicity, adjuvanticity and antigenicity of LT(R192G) and LT(R192G/L211A) by intradermal immunization in mice. PloS one 17 31682624
2017 Inactivation of TNF/LT locus alters mouse metabolic response to concentrated ambient PM2.5. Toxicology 17 28917655
2012 A functional polymorphism of lymphotoxin-alpha (LTA) gene rs909253 is associated with gastric cancer risk in an Asian population. Cancer epidemiology 17 22748850
2021 Auraptene, a Monoterpene Coumarin, Inhibits LTA-Induced Inflammatory Mediators via Modulating NF-κB/MAPKs Signaling Pathways. Evidence-based complementary and alternative medicine : eCAM 16 34824589
2018 Staphylococcal LTA antagonizes the B cell-mitogenic potential of LPS. Scientific reports 15 29367683
2015 Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System. EBioMedicine 15 26137562
2014 Intradermal administration of the Type II heat-labile enterotoxins LT-IIb and LT-IIc of enterotoxigenic Escherichia coli enhances humoral and CD8+ T cell immunity to a co-administered antigen. PloS one 15 25536061
2006 LTA recognition by bovine gammadelta T cells involves CD36. Journal of leukocyte biology 15 16551677
1995 TNFB gene polymorphism in patients with systemic lupus erythematosus in Korean. The Korean journal of internal medicine 15 7495771
2019 Time-dependent C5a and C5aR expression in dental pulp cells following stimulation with LTA and LPS. International journal of molecular medicine 14 31257457
2017 Hispolon Suppresses LPS- or LTA-Induced iNOS/NO Production and Apoptosis in BV-2 Microglial Cells. The American journal of Chinese medicine 14 29121802
2010 Relationship between TNFA, TNFB and TNFRII gene polymorphisms and outcome after unrelated hematopoietic cell transplantation in a Chinese population. Bone marrow transplantation 14 20548340
2007 Effects of LT-K63 and CpG2006 on phenotype and function of murine neonatal lymphoid cells. Scandinavian journal of immunology 14 17850587
2003 TNFB polymorphism may be associated with schizophrenia in the Korean population. Schizophrenia research 14 12648734
2015 Regulation of cell fate by lymphotoxin (LT) receptor signalling: Functional differences and similarities of the LT system to other TNF superfamily (TNFSF) members. Cytokine & growth factor reviews 13 26028499

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