CD40L/CD154/TRAP Protein, Human

"CD40 Ligand (CD40L; CD154; TRAP) belongs to the tumor necrosis factor (TNF) family, is the ligand for CD40/TNFRSF5, specifically expressed on activated CD4+ T-lymphocytes^[1].
CD40L is a type II transmembrane protein on B cells triggers important signals for B cell differentiation, maturation, and apoptosis^[4].
CD40L acts function by cross-linking on T-cells to generate a costimulatory signal and thus enhances the production of IL4 and IL10 in conjunction with the TCR/CD3 ligation and CD28 costimulation, as well as promoting the production of interferon-γ, and TNF-α^[1][4].
CD40L, binding with CD40 on antigen-presenting cells (APC), activates TNFR-associated factor 2- and IKK2-dependent pathways with stimulating I-κB kinase (IKK), increasing NF-κB DNA binding, and p65 nuclear translocation. The activation of I-κB kinase leads to strongly c-Jun N-terminal kinase activation as well as GST-I-κB and GST-p65 phosphorylation^[2].
CD40L involves in MAPK pathways that strongly repress Bcl-6 with inducing the phosphorylation of Erk1/2, p38 and Jnk1/2 and activating IRF4 mediated by NF-κB^[3].
CD40L also binds to and signals through several integrins, including αvβ3 and α5β1, which bind to the trimeric interface of CD40L. CD40L plays a major role in immune response and is a major target for inflammation^[5].
CD40L is widely found in different animals, while the the sequence in Human is highly similar to Rhesus macaque (98.08%), but very different from Rat and Mouse with similarities of 77.31% and 77.69%, respectively. CD40L in Human is cleaved into 2 chains of membrane form (1-261 a.a.) and soluble form (113-261 a.a.), while the soluble form derives from the membrane form by proteolytic processing. Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and a matrix metalloproteinases (MMP) inhibitor-sensitive pathway^[6].
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"CD40 Ligand (1 ng/mL; 24 hr) induces endothelial cell vascular cell adhesion molecule-1 (VCAM-1) expression. CD40 Ligand shows costimulation effect with IL-4 against VCAM-1^[7].
CD40 Ligand (1 ng/mL; 24 hr) combined with IL-4 enhances IL-6 and inhibits IL-8 production by HUVEC^[7].
CD40 Ligand (500 ng/mL; 72 hr) with 50 ng/mL IL-21 stimulates eripheral blood mononuclear cells (PBMCs) to secrete donor-specific antibodies (DSA)^[8].
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CD40 Ligand (2.86 ng/mL or 2.09 ng/mL) has been demonstrated to be a mark of cardiovascular risk, while the level (2.86 ng/mL) in who subsequently developed myocardial infarction, stroke, or cardiovascular death (cases) is higher than control group (2.09 ng/mL)^[8].