The CD40 receptor was first associated with expression in B cells and the role it plays through its ligand CD40L (CD154) in moderating T cell activation. Broader expression may indicate a broader role for CD40 and CD40L in immune function and disease states such as transplant rejection and HIV infection. Disruption of CD40 interaction with CD40L may prove therapeutic in the treatment of autoimmune disorders or heart disease and modulation of the interaction may in the future be exploited in cancer treatment. As a member of the TNF receptor family, CD40 relies on interaction with TRAF proteins to mediate an intracellular signal in response to CD40L binding. The pathway downstream of TRAFs activates the transcription factor NF-kappaB through a kinase pathway involving map kinases, NIK (NF-kappaB inducing kinase) and I-kappa B kinases. Some CD40 responses like regulation of immunoglobulin expression might be mediated by NF-kappaB transcriptional activation.
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