Cytokine that acts as a ligand to CD40/TNFRSF5. Costimulates T-cell proliferation and cytokine production. Its cross-linking on T-cells generates a costimulatory signal which enhances the production of IL4 and IL10 in conjunction with the TCR/CD3 ligation and CD28 costimulation. Induces the activation of NF-kappa-B. Induces the activation of kinases MAPK8 and PAK2 in T-cells. Induces tyrosine phosphorylation of isoform 3 of CD28. Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL4. Involved in immunoglobulin class switching.; Acts as a ligand for integrins, specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40 receptor are required for activation of CD40-CD40LG signaling, which have cell-type dependent effects, such as B-cell activation, NF-kappa-B signaling and anti-apoptotic signaling.

1. this study reports the clinical and CD40L genetic features of six Iranian hyper IgM syndrome patients PMID: 30081731
2. Overexpression of CD40L-WT/CD40L-M in CD40+ NSCLC cells increased SA-beta-gal staining activity and inhibited DNA synthesis and cell proliferation. PMID: 30078020
3. T cell-stimulated CLL cells actively recruited monocytes, and CD40L was identified as the responsible T-cell factor that mediated recruitment. PMID: 28971904
4. this study shows that decreased serum levels of soluble CD40L correlate in treated patients with Relapsing-Remitting Multiple Sclerosis PMID: 29050818
5. In conclusion, we described a new pathway of platelet-monocyte interaction, mediated by sCD40L and oxidative stress that may contribute to the progression of endothelial dysfunction during Shiga toxin 2-associated hemolytic uremic syndrome. PMID: 29068360
6. show that sCD40L/alpha5beta1 interaction leads to platelet activation as evaluated in the human whole blood PMID: 26719354
7. In this first X chromosome-wide association study of adult patients with IBD, we identified an IBD susceptibility locus with genome-wide significance at rs2427870 on chrXq26.3, located 66 kbp upstream of CD40LG and 83.4 kbp upstream of ARHGEF6 [OR, 1.22; combined p = 3.79 x 10-15]. PMID: 28333213
8. Study indicates that the rs1126535C/T polymorphism of CD154 gene was involved in the progression of Chinese SLE patients, probably by affecting the expression of CD154. PMID: 28550400
9. study found that plasma CD40L was associated with acute chest syndrome (ACS), and that sickle cell anemia (SCA)patients with a lifetime history of ACS (ACS+) presented significantly higher plasma CD40L and TSP-1 than patients who had never experienced ACS (ACS-) PMID: 28609750
10. this paper demonstrates importance of CD40/CD40L signaling on IL-10-producing regulatory B cells in Chinese children with Henoch-Schonlein purpura nephritis PMID: 27837410
11. Soluble CD40 ligand derived from serum is not correlated with early stage of multiple sclerosis. PMID: 28619427
12. Analysis of the early events after receptor engagement revealed that both TNF and CD40L activate the classical NF-kappaB pathway, and confirm activation of the alternative by the latter. Furthermore, using genetic and pharmacological inhibition of the classical pathway we show that activation of the alternative occurs independently of the former. This reveals insights into NF-kappaB signaling by CD40L and TNF in endoth... PMID: 29183724
13. CD40L, more than IL-6, or TNF-alpha, constitutes a predictor to explain polycystic ovary syndrome and associated features PMID: 27572328
14. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in focal segmental glomerulosclerosis. PMID: 29155846
15. Plasma sCD40L levels were elevated in systemic lupus erythematosis patients who had positive anti-phospholipid antibodies and experienced arterial thrombosis, suggesting that enhanced release of sCD40L through platelet activation presumably by aPL could contribute to the development of atherothrombotic disease. PMID: 28421990
16. Higher concentrations of CD40L in patients with limited cutaneous form in our study might suggest a role for CD40/CD40L pathway in vascular pathology of systemic sclerosis. PMID: 27392528
17. we also report for the first time that the rs1126535 C allele (CD40L gene) may predict a worse response after gastric bypass in morbidly obese patients PMID: 27681093
18. Serum levels of sCD40L and MMP-9 are associated with the stability of carotid plaques. PMID: 28642174
19. studies identify a novel molecular mechanism of regulation of CD40L by the transcription factor GLI2 in the tumor microenvironment downstream of CCR3 signaling PMID: 28461568
20. data suggest that therapeutic CD40-CD40L blocking agents may prove efficacious not only in early and established rheumatoid arthritis (RA), but also in inhibiting the progression of the disease from arthralgia or undifferentiated arthritis to RA PMID: 28455435
21. CD4(+) T cells that coexpress CD57 and CD154, which are exclusively present in cytomegalovirus-positive individuals. PMID: 27566833
22. Serum CD40L levels were elevated in both neuromyelitis optica and multiple sclerosis patients. PMID: 27725124
23. plasma PGE2 is correlated with the prevention of IVIG resistance and CAL formation through CD40L in KD PMID: 27525421
24. This study provides the first evidence that human circulating group 2 innate lymphoid cells can express CD154 and stimulate the production of IgE by B lymphocytes through IL-25/IL-33 stimulation or TLR triggering PMID: 27576126
25. data also demonstrated that the CD154-triggered inhibition of the Fas-mediated cell death response was dependent on a suppression of caspase-8 cleavage, but independent of de novo protein synthesis or alterations in Fas expression on cell surface. PMID: 27391025
26. These results suggest soluble CD40L could have a prognostic value in ST-elevation myocardial infarction patients. PMID: 27172386
27. persistence of helper T-cell-derived CD40L on or in B cells could permit sustained CD40 signaling enabling survival and proliferation of antigen-presenting B cells following brief interactions with helper T cells in vivo in germinal centers. PMID: 27753080
28. These results demonstrate the feasibility of engineered nuclease-directed gene repair to restore endogenously regulated CD40L, and the potential for its use in T-cell therapy for X-HIGM syndrome. PMID: 26903548
29. Hypertensives showed significantly enhanced soluble CD40L levels compared to normotensive controls PMID: 27090943
30. The levels of sCD40l have no influence on survival or cardiovascular events and mortality in haemodialysis patients in a long-term follow-up PMID: 27295448
31. CD40L gene polymorphism was found to be associated with severe falciparum malaria in Indian population especially in severe malarial anaemia. PMID: 28352049
32. While CD40 expression tends to be relatively high in the peritumoral dermis of epithelial carcinomas, the expression of CD40L in mast cells is low in the same peritumoral area, compared with the opposite findings in psoriasis and actinic keratosis. PMID: 28267402
33. Increased serum sCD40L levels may be related to angiogenesis in patients with multiple myeloma (MM). This protein has potential clinical usefulness in MM and may be considered as an additional prognostic marker. The correlation of sCD40L with beta-thromboglobulin may indicate that in patients with MM sCD40L derives from activated platelets. PMID: 27243341
34. Primary Aldosteronism is related to platelet activation, expressed as higher plasma values of soluble CD40L and soluble P-selectin values. PMID: 27101095
35. Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings. PMID: 27094978
36. Overexpression of CD154 on CD4(+)T cells is unlikely to be central to the pathogenesis of idopathic thrombocytopenic purpura, and other immune dysfunctions should be targeted for therapy purposes. PMID: 26183367
37. the serum levels of the soluble factors sCD40L and CXCL1 are not associated with endometriosis and are not suitable as biomarkers for disease diagnosis. PMID: 27190986
38. Increased sCD40L plasma levels are associated with the presence of insulin resistance and not the state of glucose tolerance. PMID: 26934129
39. we report that Kv1.3-NPs reduced NFAT activation and CD40L expression exclusively in CD45RO(+) T cells. Furthermore, Kv1.3-NPs suppressed cytokine release and induced a phenotype switch of T cells from predominantly memory to naive. PMID: 26994905
40. mCD40L-induced cell death mediated by NORE1A expression appeared to be independent of mCD40L-induced cell death mediated by sustained JNK activation since NORE1A inhibition did not affect JNK phosphorylation and vice versa PMID: 26986513
41. diagnostic value of soluble CD40 ligand (sCD40L) and vascular endothelial growth factor (VEGF) for Alzheimer's disease PMID: 26706786
42. Study allows identify significant different genetic heterogeneity between two investigated populations (France and Tunisia) and revealed discrepancies in the prevalence of CD40LG polymorphisms that may be explained by ethnic and geographic differences. PMID: 26577033
43. concentrations of the C-reactive protein, myeloperoxidase and soluble CD40 ligand taken from peripheral vein were closely similar to the concentration found in coronary blood of ACS patients PMID: 26576922
44. Studies suggest that the CD40/CD154 pathway represents a promising potential therapeutic target for the prevention of transplantation rejection. PMID: 26268734
45. Three single-nucleotide polymorphisms (SNPs) of the TLR8, CD40LG and IRAK1 genes on the X chromosome were genotyped. PMID: 26043172
46. plasma soluble CD40L levels are reduced by antiplatelet therapy with clopidogrel, but not associated with long-term ischemic outcomes in unselected consecutive aspirin-treated patients undergoing cardiac catheterization. PMID: 26237513
47. The study findings showed that plasma sCD40L, fetuin-A, and PAPP-A levels are associated with carotid plaque formation and instability. PMID: 26214492
48. CD40 ligand induces RIP1-dependent, necroptosis-like cell death in low-grade serous but not serous borderline ovarian tumor cells. PMID: 26313915
49. CD40 ligand induces von Willebrand factor release from endothelial cells PMID: 25608503
50. Higher plasma soluble CD40L levels on presentation are associated with clinical severity and have potential to be a good prognostic biomarker of aneurysmal subarachnoid hemorrhage. PMID: 25944664

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Cell membrane; Single-pass type II membrane protein. Cell surface.; [CD40 ligand, soluble form]: Secreted.

Tumor necrosis factor family

Specifically expressed on activated CD4+ T-lymphocytes.

HGNC: 11935

OMIM: 300386

KEGG: hsa:959

STRING: 9606.ENSP00000359663

UniGene: Hs.592244