Affinage

CD40

Tumor necrosis factor receptor superfamily member 5 · UniProt P25942

Length
277 aa
Mass
30.6 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD40 is a type I transmembrane glycoprotein of the TNFR superfamily that functions as a co-stimulatory receptor coordinating adaptive and innate immune responses upon engagement by its ligand CD40L (CD154) (PMID:7516669). First identified as the B cell surface antigen Bp50 that augments proliferation of activated B cells (PMID:3487090), CD40 lacks intrinsic kinase activity and signals through ligand-induced receptor multimerization: the trimerized cytoplasmic domain recruits a complex containing TRAF2, TRAF3, TRAF5, TRAF6, and c-IAP1 to drive NF-κB and downstream kinase activation (PMID:11562359). Distinct TRAF branches partition CD40 outputs—TRAF6 recruits Tpl2 to selectively activate ERK and IgE induction without affecting B cell proliferation (PMID:12881420), TRAF5 mediates a separate subset of proliferative and surface-marker responses (PMID:10449775), and NEDD4-driven K63-ubiquitination of TRAF3 is required for AKT activation and immunoglobulin class switching via AID (PMID:25072696). Signaling magnitude is restrained by the negative regulator Act1 (PMID:15485634), while the transcription factor AKNA coordinately activates both CD40 and CD40L promoters (PMID:11268217). In the immune system, CD40 engagement on antigen-presenting cells upregulates B7.2 to license T cell priming (PMID:8791591), enhances B cell antigen processing (PMID:8566008), and in cDC1s induces Bcl-xL (Bcl2l1) to sustain dendritic cell survival during anti-tumor CD8 T cell priming (PMID:36271147). Beyond lymphocytes, CD40 is functional on endothelial cells—where it induces adhesion molecules, leukocyte recruitment, and VEGF-dependent angiogenesis (PMID:7540655, PMID:12874247)—as well as on macrophages where CD40-TRAF6 signaling drives atherosclerotic monocyte recruitment (PMID:29406859), on neurons where it promotes survival via MAPK signaling (PMID:11847112), and on islet beta-cells and neutrophils that mount inflammatory responses through ERK/NF-κB and PI3K/Akt pathways (PMID:16936191, PMID:18289643).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1986 High

    Established CD40 (Bp50) as a functional B cell surface molecule delivering activation co-signals, answering whether this antigen had a regulatory role rather than being a passive marker.

    Evidence Monoclonal antibody stimulation and proliferation assays on purified resting versus activated B cells

    PMID:3487090

    Open questions at the time
    • Receptor identity and ligand unknown at this stage
    • No molecular signaling mechanism defined
  2. 1991 High

    Defined the immediate biochemical signaling response to CD40 engagement, showing it triggers tyrosine phosphorylation, phosphoinositide turnover, and serine/threonine kinase cascades.

    Evidence In vitro kinase assays, phosphoinositide turnover, and kinase inhibitor studies in B-lineage cells

    PMID:1716631

    Open questions at the time
    • Specific kinases and adaptors not molecularly identified
    • Link to transcriptional output not established
  3. 1994 High

    Established CD40 as a TNFR-superfamily receptor for CD40L and linked CD40-IL-4/IL-13 co-stimulation to IgE isotype switching, defining its molecular identity and a functional output.

    Evidence Recombinant protein studies, gene mapping, and B cell stimulation/isotype switching assays (review of multiple studies)

    PMID:7516669

    Open questions at the time
    • Cytoplasmic signaling adaptors not yet identified
    • Structural basis of receptor activation unresolved
  4. 1995 High

    Extended CD40 function beyond lymphocytes by showing endothelial CD40 drives adhesion molecule expression and leukocyte adhesion, and demonstrated CD40 augments B cell antigen processing independent of proliferation.

    Evidence Soluble CD40L stimulation with blocking antibodies on endothelium; T cell hybridoma activation assays with CD40L-expressing cells

    PMID:7540655 PMID:8566008

    Open questions at the time
    • Intracellular signaling mediators in endothelium not defined
    • Antigen-processing step affected by CD40 not molecularly identified
  5. 1996 High

    Placed CD40 upstream of B7-CD28 co-stimulation in T cell priming and identified TRAF5 as a specific downstream mediator, beginning the dissection of branched CD40 outputs.

    Evidence CD40L-knockout mouse reconstitution with activating anti-CD40 plus anti-B7 blockade; TRAF5 knockout B cell phenotyping

    PMID:10449775 PMID:8791591

    Open questions at the time
    • How TRAF5 selectively mediates a subset of signals while NF-κB/JNK remain intact unexplained
    • Other TRAF contributions not yet resolved
  6. 2001 High

    Defined the core activation mechanism—ligand-induced multimerization recruiting a TRAF2/3/5/6/c-IAP1 complex—and identified AKNA as a coordinate transcriptional regulator of CD40 and CD40L.

    Evidence Defined multimeric cytoplasmic-domain constructs with NF-κB reporters and complex co-isolation; promoter-binding and reporter assays for AKNA

    PMID:11268217 PMID:11562359

    Open questions at the time
    • Stoichiometry and structure of the receptor-TRAF complex not resolved
    • How distinct TRAFs route to distinct outputs not fully defined
  7. 2002 High

    Demonstrated a non-immune role for CD40 in neuronal survival, showing CD40 signaling activates p44/42 MAPK and protects neurons, with CD40 loss causing progressive neuronal dysfunction.

    Evidence MAPK/JNK assays in neuronal cells plus CD40 knockout mouse brain phenotyping

    PMID:11847112

    Open questions at the time
    • Ligand source for neuronal CD40 in vivo unclear
    • Adaptor usage in neurons not defined
  8. 2003 High

    Dissected endothelial CD40 signaling branches, establishing CD40-induced VEGF-dependent angiogenesis and an NF-κB-independent route to tissue factor, refining how CD40 outputs are pathway-partitioned.

    Evidence SCID mouse skin engraftment with anti-VEGF blockade; A20 overexpression dissecting NF-κB-dependent versus independent CD40 outputs

    PMID:12874247 PMID:12885753

    Open questions at the time
    • The non-NF-κB pathway driving tissue factor not identified
    • Receptor-proximal events for angiogenic gene induction undefined
  9. 2003 High

    Identified Tpl2 as the kinase selectively coupling CD40-TRAF6 to ERK activation, dissociating ERK-dependent IgE induction from proliferation and providing a molecular basis for branched signaling.

    Evidence Tpl2 knockout mice, CD40/TRAF6/Tpl2 co-immunoprecipitation, and TRAF6 overexpression epistasis with Ig production assays

    PMID:12881420

    Open questions at the time
    • How TRAF6 selectively engages Tpl2 versus other effectors unresolved
    • Contribution to other CD40 outputs not mapped
  10. 2004 Medium

    Established Act1 as a negative regulator restraining CD40 signaling and showed CD40 signaling is largely silent in germinal center B cells, revealing how CD40 output is gated in space and intensity.

    Evidence Act1 and CD40-Act1 double knockout epistasis with signaling readouts; CD40 gene-expression signature and NF-κB localization in lymphoid tissue

    PMID:15331443 PMID:15485634

    Open questions at the time
    • Molecular mechanism by which Act1 dampens the complex not fully defined
    • What suppresses CD40 signaling within germinal centers unknown
  11. 2006 High

    Revealed CD40L can signal independently of CD40 by binding integrin α5β1, and extended CD40-driven inflammation to islet beta-cells via ERK/NF-κB chemokine induction.

    Evidence Solid-phase binding with purified α5β1 and downstream ERK/IL-8 assays; islet stimulation with ERK and NF-κB inhibitors

    PMID:16936191 PMID:17182621

    Open questions at the time
    • Relative in vivo contribution of CD40 versus α5β1 ligation unclear
    • Receptor-proximal adaptors in islet beta-cells not defined
  12. 2007 Medium

    Defined a redox-sensitive PI3K/Akt/NF-κB axis amplifying CD40L signaling in endothelium and a platelet-neutrophil CD40-CD40L feedback loop, linking CD40 to thrombo-inflammatory amplification.

    Evidence Adenoviral Akt/p38 manipulation and PI3K inhibitors with NF-κB translocation readouts; neutrophil/platelet ROS and conjugate assays with PI3K inhibitor and ROS scavenger

    PMID:17459878 PMID:18289643

    Open questions at the time
    • How PI3K/Akt couples to the receptor-TRAF complex in these cells not defined
    • In vivo relevance of the redox feedback loop not established
  13. 2014 High

    Identified NEDD4 as an E3 ligase that K63-ubiquitinates TRAF3 to enable CD40-driven AKT activation and class switching, connecting a specific ubiquitin event to a distinct signaling branch.

    Evidence Co-IP, K63-linkage ubiquitin analysis, NEDD4 loss-of-function, and AKT/AID/class-switch readouts

    PMID:25072696

    Open questions at the time
    • Structural detail of NEDD4-CD40 interaction not resolved
    • How TRAF3 ubiquitination is integrated with other branches unclear
  14. 2015 Medium

    Validated the CD40-TRAF6 protein-protein interface as a druggable node by showing small-molecule inhibitors block binding and reduce inflammation in vivo.

    Evidence In silico docking, in vitro interaction assays, and peritonitis/sepsis mouse models

    PMID:25622654

    Open questions at the time
    • Single-lab validation of specificity
    • Off-target effects not exhaustively excluded
  15. 2018 High

    Demonstrated selective CD40-TRAF6 blockade reduces atherosclerosis by limiting monocyte recruitment without impairing T cell or humoral immunity, establishing branch-selective therapeutic targeting.

    Evidence TRAF-STOP small molecules, Apoe-/- atherosclerosis models, transcriptional profiling, and NF-κB signaling assays

    PMID:29406859

    Open questions at the time
    • Long-term safety of chronic CD40-TRAF6 inhibition unknown
    • Macrophage-intrinsic versus systemic contributions not fully separated
  16. 2022 High

    Showed CD40-induced Bcl-xL (Bcl2l1) sustains cDC1 survival to enable anti-tumor CD8 T cell priming, defining a survival output of CD40 in dendritic cells.

    Evidence cDC1-specific CD40 knockout, Bcl2l1 re-expression rescue, mitochondrial potential and caspase assays, and tumor rejection models

    PMID:36271147

    Open questions at the time
    • Receptor-proximal events driving Bcl2l1 induction in cDC1 not mapped
    • Generalizability to other dendritic cell subsets unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct TRAF/adaptor configurations and post-translational modifications are integrated at the multimerized receptor to select cell-type-specific outputs remains incompletely resolved.
  • No high-resolution structure of the assembled CD40-TRAF signaling complex in the corpus
  • Quantitative rules linking receptor occupancy to branch selection undefined
  • Mechanism of context-dependent output across cell types not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1643685 Disease 2
Partners
CD40LGITGA5NEDD4TRAF1TRAF2TRAF3TRAF5TRAF6
Complex memberships
CD40-TRAF signaling complex (TRAF2/TRAF3/TRAF5/TRAF6/c-IAP1)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 CD40 (Bp50), a 50-kDa surface antigen expressed on all B cells, delivers positive signals that stimulate activated B cells to traverse the cell cycle; anti-Bp50 alone does not activate resting B cells but augments proliferation when combined with anti-Bp35 or anti-immunoglobulin, functioning similarly to B cell growth factor on activated but not resting B cells. Monoclonal antibody stimulation assays, B cell proliferation assays with purified resting vs. activated B cells, F(ab')2 fragment experiments Proceedings of the National Academy of Sciences of the United States of America High 3487090
1991 CD40 receptor engagement on B-lineage cells (pro-B through activated mature B cells, but not resting mature B cells) stimulates tyrosine phosphorylation of four substrates (67, 72, 96, 113 kDa), induces rapid IP3 production (phosphoinositide turnover), and activates five distinct serine/threonine kinases; tyrosine kinase inhibitors (genistein, herbimycin A) blocked both tyrosine phosphorylation and downstream PI turnover and serine/threonine kinase activation. In vitro kinase assays, phosphoinositide turnover measurement, kinase inhibitor studies (H7, genistein, herbimycin A), immunoprecipitation The Journal of biological chemistry High 1716631
1994 CD40 is a 277-aa, 45–50 kDa type I transmembrane glycoprotein member of the TNFR superfamily; its gene maps to human chromosome 20q11-2–q13-2; it binds CD40-L (a ~35 kDa TNF superfamily member encoded on Xq24); cross-linking CD40 with immobilized anti-CD40 or CD40-L-expressing cells drives B cell proliferation, and in combination with IL-4 or IL-13 generates long-term B cell lines with IgE isotype switching. Recombinant protein studies, B cell stimulation assays, gene mapping, molecular characterization Annual review of immunology High 7516669
1995 Vascular endothelial cells express functional CD40; ligation of endothelial CD40 by soluble recombinant CD40 ligand (sgp39) activates endothelial cells, inducing E-selectin, ICAM-1, and augmenting VCAM-1 expression, leading to leukocyte adhesion; these effects are blocked by anti-gp39 mAb, anti-CD40 mAb, or soluble CD40. Soluble recombinant CD40L stimulation of endothelial cells, adhesion molecule expression assays, blocking antibody experiments, tissue immunostaining The Journal of experimental medicine High 7540655
1996 CD40-dependent T cell priming and activation occurs through CD40 signaling in antigen-presenting cells to upregulate B7.2 costimulatory molecules; reconstitution of CD40L-deficient mice with an activating anti-CD40 antibody (which increased B7.2 on spleen cells) restored both cytotoxic T cell and T cell-dependent B cell responses; these were abrogated by anti-B7 antibodies, placing B7-CD28 downstream of CD40 in T cell priming. CD40L-knockout mouse model, antibody reconstitution experiments, anti-B7 blockade, in vivo gene transfer model Science (New York, N.Y.) High 8791591
1996 TRAF5 is required for CD40-mediated B cell proliferation and upregulation of CD23, CD54, CD80, CD86, and Fas, as well as for CD40-stimulated IgE production with IL-4; TRAF5-deficient B cells show defects in these responses despite intact NF-κB and JNK activation by CD40, indicating TRAF5 mediates a distinct subset of CD40 signals. TRAF5 gene-targeted knockout mice, B cell proliferation assays, surface molecule expression analysis by flow cytometry, in vitro Ig production assays Proceedings of the National Academy of Sciences of the United States of America High 10449775
2001 CD40 signal transduction is initiated by receptor multimerization upon ligand binding; trimeric (but not monomeric) CD40 cytoplasmic domain activates NF-κB; the multimerized cytoplasmic domain forms complexes containing TRAF2, TRAF3, TRAF5, TRAF6, and c-IAP1; c-IAP1 association is indirect and depends on intact TRAF1/2/3 binding site. Defined multimeric constructs of CD40 cytoplasmic domain (soluble and myristoylated), NF-κB reporter assays in HEK293 cells, co-isolation and identification of signaling complexes, point mutations in TRAF binding sites The Journal of biological chemistry High 11562359
2003 Tpl2 kinase is selectively required for CD40-mediated ERK activation in B cells and macrophages; Tpl2 is recruited to a CD40/TRAF6 complex upon CD40 stimulation; TRAF6 overexpression activates ERK in a Tpl2-dependent manner; loss of ERK (via Tpl2 knockout) impairs CD40-mediated IgE induction but not B cell proliferation, dissociating these two downstream outcomes. Tpl2 knockout mice, ERK/JNK/p38 activation assays, NF-κB activation assays, co-immunoprecipitation of CD40/TRAF6/Tpl2 complex, TRAF6 overexpression in Tpl2-/- cells, Ig production assays The EMBO journal High 12881420
2004 Act1, a novel adaptor molecule, negatively regulates CD40 and BAFFR signaling in B cells; Act1-deficient B cells show enhanced CD40-mediated survival with stronger IκB phosphorylation, NF-κB2 processing, and JNK/ERK/p38 activation; the autoimmune phenotype of Act1-deficient mice is blocked in CD40-Act1 double knockouts, placing Act1 as a negative regulator downstream of CD40. Act1 knockout mice, CD40-Act1 double knockout epistasis, B cell survival assays, IκB phosphorylation and NF-κB2 processing assays, MAPK activation assays Immunity High 15485634
2004 CD40 signaling is absent in most germinal center (GC) B cells despite being required for pre- and post-GC stages; NF-κB transcription factors remain cytoplasmic in most GC B cells after CD40 stimulation, indicating lack of active CD40 signaling during GC expansion, with only a subset of centrocytes showing nuclear NF-κB. DNA microarray gene expression signature of CD40 signaling, NF-κB nuclear translocation analysis by immunostaining in lymphoid tissues, in vitro CD40 stimulation of transformed GC B cells Blood Medium 15331443
2001 AKNA, an AT-hook transcription factor, directly binds the A/T-rich regulatory elements of both CD40 and CD40L promoters and coordinately regulates their expression; AKNA is a nuclear protein with PEST motifs expressed mainly in B and T lymphocytes and dendritic cells, predominantly in germinal center B cells. Promoter-binding assays, reporter gene assays, subcellular localization studies, expression analysis during B cell differentiation Nature High 11268217
2014 NEDD4, an HECT-family E3 ubiquitin ligase, constitutively interacts with CD40 and mediates K63-linked ubiquitination of TRAF3; this TRAF3 ubiquitination is required for CD40-mediated AKT activation and modulates immunoglobulin class switching through regulation of activation-induced cytidine deaminase (AID) expression. Co-immunoprecipitation, ubiquitin chain-type analysis (K63-linkage), NEDD4 knockout/knockdown, AKT phosphorylation assays, AID expression analysis, class switch assays Nature communications High 25072696
2018 CD40-TRAF6 signaling in macrophages promotes atherosclerosis by driving CD40 and β2-integrin expression on classical monocytes, enhancing monocyte recruitment; small molecule TRAF-STOPs that selectively block CD40-TRAF6 (but not CD40-TRAF2/3/5) interactions reduce atherosclerosis and macrophage activation via reduced canonical NF-κB pathway phosphorylation, without impairing T cell proliferation, Ig isotype switching, or germinal center formation. TRAF-STOP small molecule inhibitors, Apoe-/- mouse atherosclerosis models, transcriptional profiling, NF-κB signaling assays, rHDL nanoparticle-targeted delivery, flow cytometry, in vitro macrophage migration/activation assays Journal of the American College of Cardiology High 29406859
2015 Small molecule CD40-TRAF6 inhibitors identified by in silico docking block the physical interaction between CD40 cytoplasmic domain and TRAF6, reducing inflammation in peritonitis and sepsis mouse models without apparent side effects; this validates the CD40-TRAF6 protein-protein interaction as a tractable drug target. Computational docking, in vitro protein interaction assays, in vivo mouse models of peritonitis and sepsis Journal of chemical information and modeling Medium 25622654
2022 CD40 signaling in classical type 1 dendritic cells (cDC1s) induces expression of Cd70, Tnfsf9 (4-1BBL), Ptgs2 (COX-2), and Bcl2l1 (Bcl-xL); CD40-induced Bcl2l1 is required for cDC1 survival during anti-tumor CD8 T cell priming by maintaining mitochondrial membrane potential and preventing caspase activation in tumor-draining lymph nodes; re-expression of Bcl2l1 in Cd40-/- cDC1s reverses impaired antigen presentation. cDC1-specific CD40 knockout mice, Bcl2l1 re-expression rescue experiment, mitochondrial transmembrane potential assay, caspase activation assay, in vitro antigen presentation assays, tumor rejection models Nature immunology High 36271147
2002 CD40 is expressed and functional on neuronal cells; CD40 ligation activates p44/42 MAPK in neurons, opposes JNK phosphorylation induced by NGF withdrawal, and protects neuronal cells from NGF- or serum withdrawal-induced injury; adult CD40-deficient mice show progressive neuronal dysfunction including reduced neurofilament isoforms, decreased Bcl-xL:Bax ratio, increased DNA fragmentation, and gross brain abnormality by 16 months. RT-PCR, western blot, immunofluorescence, MAPK activation assays, JNK assays, CD40 knockout mice, neuronal survival assays The EMBO journal High 11847112
2006 Soluble CD40L (sCD40L) binds directly to integrin α5β1 on monocytic U937 cells in a CD40- and αIIbβ3-independent manner; this binding induces translocation of α5β1 to Triton X-100-insoluble membrane fractions, activates ERK1/2 MAPK, and induces IL-8 gene expression; direct binding of sCD40L to purified α5β1 was confirmed in a solid-phase binding assay; sCD40L can simultaneously bind CD40 and α5β1 as they are independent binding interactions. Blocking antibody experiments, solid-phase binding assay with purified protein, lipid raft fractionation, ERK1/2 activation assays, IL-8 gene expression assays, α5β1-negative BJAB cell controls The Journal of biological chemistry High 17182621
2003 CD40 ligation on endothelial cells induces expression of angiogenesis factors including VEGF, FGF-2, Flt-1, and Flt-4; in vivo injection of CD40L-expressing fibroblasts into human skin engrafted on SCID mice induces marked angiogenesis dependent on VEGF (blocked by anti-VEGF treatment), establishing CD40/CD40L as a VEGF-dependent proangiogenic pathway. Anti-CD40 antibody stimulation of cultured endothelial cells, SCID mouse human skin engraftment model, anti-VEGF blocking experiment, immunohistochemistry Journal of immunology (Baltimore, Md. : 1950) High 12874247
2003 A20 overexpression in endothelial cells blocks CD40-induced NF-κB activation (upstream of IκBα degradation) and suppresses ICAM-1, VCAM-1, and E-selectin upregulation, but does not block CD40-induced tissue factor (TF) transcription, indicating CD40 induces TF through a non-NF-κB pathway; A20 also protects from CD40-mediated endothelial apoptosis. Transient transfection with CD40 and A20 expression constructs, NF-κB reporter assays, Western blot for IκBα, flow cytometry for adhesion molecules, colorimetric TF assay, RT-PCR, DNA content analysis for apoptosis Circulation High 12885753
2006 CD40 ligation on pancreatic islet beta-cells activates ERK1/2 and NF-κB signaling pathways, inducing secretion of IL-6, IL-8, MCP-1, and MIP-1β (a chemokine not previously known to be produced by islets) and upregulation of ICAM-1; ERK and NF-κB inhibitors suppress cytokine/chemokine production, establishing these pathways as the mechanism of CD40-driven islet inflammation. CD40L stimulation of human and nonhuman primate islets and NIT-1 insulinoma cells, ELISA, quantitative RT-PCR, double-immunofluorescence, ERK1/2 and NF-κB pathway inhibitors Diabetes High 16936191
2007 CD40L-induced CD40L synthesis and MCP-1 release by endothelial cells is mediated through a redox-sensitive PI3K/Akt/NF-κB signaling axis; pharmacological inhibition of PI3K and p38 MAPK, and adenoviral inactivation of Akt and p38, blocked these effects; Akt overexpression augmented nuclear NF-κB translocation induced by CD40L, while Akt inactivation inhibited it. Pharmacological inhibitors (LY294002 for PI3K), adenoviral Akt and p38 overexpression/inactivation, confocal microscopy of NF-κB nuclear translocation, MCP-1 ELISA The Journal of biological chemistry High 17459878
1995 CD40 ligation on B cells stimulates antigen processing; co-culture of B cells with CD40L-expressing insect cells or anti-CD40 mAb augments activation of antigen-specific T cell hybridomas at lower antigen doses; this effect is on an intracellular processing step (not peptide presentation directly), is independent of B7, LFA-1, or CD23 upregulation, and does not require B cell proliferation. T cell hybridoma activation assays, co-culture with CD40L-expressing insect cells, anti-CD40 mAb, peptide presentation controls, flow cytometry for surface molecules European journal of immunology Medium 8566008
2008 Neutrophils express CD40 (confirmed by RT-PCR and Western blot); platelet-neutrophil CD40-CD40L interaction enhances stimulation-induced platelet sCD40L release and augments neutrophil superoxide/ROS generation; this process is mediated via the PI3K/Akt pathway and forms a redox-controlled positive feedback loop where ROS further amplifies platelet sCD40L release. RT-PCR and Western blot for CD40 on neutrophils, ELISA for sCD40L, chemiluminescence and confocal microscopy for superoxide, flow cytometry for platelet-neutrophil conjugates, PI3K inhibitor (LY294002), N-acetylcysteine ROS scavenger, anti-CD40L blocking antibody Thrombosis research Medium 18289643

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 CD40 and CD154 in cell-mediated immunity. Annual review of immunology 1166 9597126
2000 CD40-CD40 ligand. Journal of leukocyte biology 1131 10647992
1994 The CD40 antigen and its ligand. Annual review of immunology 1094 7516669
2001 The CD40/CD154 receptor/ligand dyad. Cellular and molecular life sciences : CMLS 610 11229815
2004 CD40/CD154 interactions at the interface of tolerance and immunity. Annual review of immunology 522 15032580
1996 Immune regulation by CD40 and its ligand GP39. Annual review of immunology 504 8717526
1986 Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proceedings of the National Academy of Sciences of the United States of America 496 3487090
2001 CD40 signaling and plaque instability. Circulation research 483 11739273
2019 CD40 Agonist Antibodies in Cancer Immunotherapy. Annual review of medicine 440 31412220
1996 CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America 409 8637903
1995 Expression of functional CD40 by vascular endothelial cells. The Journal of experimental medicine 362 7540655
2013 Agonistic CD40 antibodies and cancer therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 358 23460534
2009 The role of CD40 and CD154/CD40L in dendritic cells. Seminars in immunology 348 19524453
1996 CD40 ligand-dependent T cell activation: requirement of B7-CD28 signaling through CD40. Science (New York, N.Y.) 320 8791591
2009 The CD40/CD40 ligand system: linking inflammation with atherothrombosis. Journal of the American College of Cardiology 303 19679244
1987 Augmentation of normal and malignant B cell proliferation by monoclonal antibody to the B cell-specific antigen BP50 (CDW40). Journal of immunology (Baltimore, Md. : 1950) 175 3492534
2018 Targeting CD40-Induced TRAF6 Signaling in Macrophages Reduces Atherosclerosis. Journal of the American College of Cardiology 165 29406859
1999 Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation. Proceedings of the National Academy of Sciences of the United States of America 152 10449775
2007 Prospect of targeting the CD40 pathway for cancer therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 150 17317815
2007 TRAF proteins in CD40 signaling. Advances in experimental medicine and biology 147 17633023
2002 CD40-CD40L interactions in atherosclerosis. Trends in cardiovascular medicine 147 11796241
1991 Stimulation of protein tyrosine phosphorylation, phosphoinositide turnover, and multiple previously unidentified serine/threonine-specific protein kinases by the Pan-B-cell receptor CD40/Bp50 at discrete developmental stages of human B-cell ontogeny. The Journal of biological chemistry 147 1716631
1995 CD40 expression by human fibroblasts. Clinical immunology and immunopathology 146 7554483
2004 Tracking CD40 signaling during germinal center development. Blood 145 15331443
2003 Prospects for CD40-directed experimental therapy of human cancer. Cancer gene therapy 143 12489023
1996 Functions of CD40 and its ligand, gp39 (CD40L). Critical reviews in immunology 139 8809473
2009 CD40/CD40L signaling and its implication in health and disease. BioFactors (Oxford, England) 134 19904719
2003 Tpl2 transduces CD40 and TNF signals that activate ERK and regulates IgE induction by CD40. The EMBO journal 133 12881420
2013 The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy. Current opinion in immunology 132 23414607
1997 The CD40 pathway in allograft rejection, acceptance, and tolerance. Current opinion in immunology 125 9368772
1996 Human dendritic cells activate T lymphocytes via a CD40: CD40 ligand-dependent pathway. European journal of immunology 122 8647193
2008 CD40-CD40 ligand interactions in oxidative stress, inflammation and vascular disease. Trends in molecular medicine 119 18977174
2004 Act1, a negative regulator in CD40- and BAFF-mediated B cell survival. Immunity 115 15485634
2009 The multi-functionality of CD40L and its receptor CD40 in atherosclerosis. Thrombosis and haemostasis 114 19652870
2003 CD40 and dendritic cell function. Critical reviews in immunology 114 12906261
2011 The CD40-CD40L system in cardiovascular disease. Annals of medicine 112 21244217
2005 CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion. Circulation 105 15795333
1996 CD40 expression by human peripheral blood eosinophils. The Journal of clinical investigation 105 8601642
2000 Chemokines and CD40 expression in human fibroblasts. European journal of immunology 104 10741409
2007 CD40 and its ligand in atherosclerosis. Trends in cardiovascular medicine 103 17482093
2002 CD40 is expressed and functional on neuronal cells. The EMBO journal 101 11847112
2004 Upregulation of the CD40/CD40 ligand dyad and platelet-monocyte aggregation in cigarette smokers. Circulation 96 15078798
1997 CD40 and CD40 ligand (CD154) are coexpressed on microvessels in vivo in human cardiac allograft rejection. Transplantation 95 9422418
2013 CD40 immunotherapy for pancreatic cancer. Cancer immunology, immunotherapy : CII 93 23589109
2000 CD154 (CD40 ligand). The international journal of biochemistry & cell biology 92 10856699
2017 Functions of CD40 and Its Ligand, gp39 (CD40L). Critical reviews in immunology 90 29773027
2001 Signaling by CD40 and its mimics in B cell activation. Immunologic research 90 11594459
2021 Agonistic CD40 Antibodies in Cancer Treatment. Cancers 87 33804039
2006 CD40 ligand binds to alpha5beta1 integrin and triggers cell signaling. The Journal of biological chemistry 87 17182621
2005 Platelet activation and the CD40/CD40 ligand pathway: mechanisms and implications for human disease. Critical reviews in immunology 86 15952932
1997 Functional role of CD40 and its ligand. International archives of allergy and immunology 85 9250584
1987 Synergistic interaction between interleukin 4 and anti-Bp50 (CDw40) revealed in a novel B cell restimulation assay. European journal of immunology 84 3500063
2007 CD40/CD40L system and vascular disease. Internal and emergency medicine 77 18043876
2001 Regulation of CD40 and CD40 ligand by the AT-hook transcription factor AKNA. Nature 73 11268217
2007 CD40-40L signaling in vascular inflammation. The Journal of biological chemistry 72 17459878
2003 Delineation of a novel pathway that regulates CD154 (CD40 ligand) expression. Molecular and cellular biology 71 12509450
2002 Inhibition of CD40 expression and CD40-mediated dendritic cell function by tumor-derived IL-10. International journal of cancer 71 12209589
2011 CD40 ligand: a neo-inflammatory molecule in vascular diseases. Immunobiology 70 21529993
2011 CD40/CD40 ligand interactions in immune responses and pulmonary immunity. Nagoya journal of medical science 68 21928689
1988 Soluble CD23 is released by B lymphocytes cycling in response to interleukin 4 and anti-Bp50 (CDw40). European journal of immunology 68 2965643
2000 Role for CD40-CD40 ligand interactions in the immune response to solid tumours. Molecular immunology 67 11163401
2003 A20 protects from CD40-CD40 ligand-mediated endothelial cell activation and apoptosis. Circulation 64 12885753
1997 Bidirectional regulation of human B cell responses by CD40-CD40 ligand interactions. Journal of immunology (Baltimore, Md. : 1950) 63 9144474
2002 The CD154-CD40 costimulatory pathway in transplantation. Transplantation 62 11810060
2008 Neutrophil CD40 enhances platelet-mediated inflammation. Thrombosis research 61 18289643
2003 Proangiogenic function of CD40 ligand-CD40 interactions. Journal of immunology (Baltimore, Md. : 1950) 61 12874247
2022 Mechanisms of CD40-dependent cDC1 licensing beyond costimulation. Nature immunology 57 36271147
2015 Discovery of small molecule CD40-TRAF6 inhibitors. Journal of chemical information and modeling 57 25622654
1999 CD40 expression in bladder cancer. The Journal of pathology 57 10398138
1995 Inhibition of the CD40-CD40ligand pathway prevents murine membranous glomerulonephritis. Kidney international 57 7564113
1993 Role of CD40-CD40-ligand interaction in Ig-isotype switching. Current opinion in immunology 57 7507684
2019 Concepts for agonistic targeting of CD40 in immuno-oncology. Human vaccines & immunotherapeutics 56 31403344
2006 CD40-CD40 ligand interaction activates proinflammatory pathways in pancreatic islets. Diabetes 55 16936191
2001 Role of CD40-CVD40L in mouse severe malaria. The American journal of pathology 54 11485931
2015 Update on CD40 and CD154 blockade in transplant models. Immunotherapy 52 26268734
2009 The Janus faces of CD40 in cancer. Seminars in immunology 52 19647448
2004 The role of CD40 ligand in systemic lupus erythematosus. Lupus 52 15230296
2000 The emerging role of CD40 ligand in HIV infection. Journal of leukocyte biology 51 10985254
2022 CD40-CD40L in Neurological Disease. International journal of molecular sciences 50 35456932
2001 Regulation of CD40 ligand expression in systemic lupus erythematosus. Current opinion in rheumatology 50 11604589
2016 miRNA-145 inhibits VSMC proliferation by targeting CD40. Scientific reports 49 27731400
2006 CD40-CD40 ligand mediates the recruitment of leukocytes and platelets in the inflamed murine colon. Gastroenterology 49 17324402
2008 Anthocyanin attenuates CD40-mediated endothelial cell activation and apoptosis by inhibiting CD40-induced MAPK activation. Atherosclerosis 47 18495129
2004 CD40 ligand gene and Kawasaki disease. European journal of human genetics : EJHG 47 15367912
1994 Regulation of CD40 ligand expression and use of recombinant CD40 ligand for studying B cell growth and differentiation. Seminars in immunology 47 7865800
2014 NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation. Nature communications 46 25072696
1998 Coexpression of CD40 and CD40 ligand in B-cell lymphoma cells. British journal of haematology 46 9792321
1997 Endothelial expression of CD40 in renal cell carcinoma. Cancer research 46 9041191
1999 CD30/CD30 ligand and CD40/CD40 ligand in malignant lymphoid disorders. The International journal of biological markers 45 10569134
2003 Differential regulation of cell survival by CD40. Apoptosis : an international journal on programmed cell death 44 12510151
2000 Expression of CD40 and CD40 ligand in the human conjunctival epithelium. Investigative ophthalmology & visual science 44 10634610
2008 A functional TNFRSF5 gene variant is associated with risk of lymphoma. Blood 43 18287517
2000 Immune regulation by CD40-CD40-l interactions - 2; Y2K update. Frontiers in bioscience : a journal and virtual library 42 11056083
2001 Molecular characterization of CD40 signaling intermediates. The Journal of biological chemistry 41 11562359
2000 CD40 ligand in CLL pathogenesis and therapy. Leukemia & lymphoma 39 11042507
2007 Blockade of CD40/CD40 ligand interactions attenuates skin fibrosis and autoimmunity in the tight-skin mouse. Annals of the rheumatic diseases 38 17823201
2023 Harnessing the potential of CD40 agonism in cancer therapy. Cytokine & growth factor reviews 37 38102001
1995 CD40-CD40 ligand interactions stimulate B cell antigen processing. European journal of immunology 37 8566008
2010 Biology and clinical applications of CD40 in cancer treatment. Seminars in oncology 36 21074067
2001 Coexpression of CD40 and CD40 ligand in cutaneous T-cell lymphoma (mycosis fungoides). Cancer research 36 11212229

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