CD40 SIGNALING IN GRAVES’ DISEASE IS MEDIATED THROUGH CANONICAL AND NON-CANONICAL THYROIDAL NF-κB ACTIVATION

CD40, a tumor necrosis factor receptor, is a major immune-modulating susceptibility gene for Graves’ disease (GD) as well as for a variety of other autoimmune diseases. Its broad association with autoimmunity underscores its paramount role in the development of a normal adaptive immune response, primarily in coordinating effective antigen presentation. The molecular pathways by which CD40 activation in the thyroid induces GD are unknown. In this study, we investigated whether NF-κB, a ubiquitious family of transcription factors, mediates the downstream effects of thyroid-specific CD40 activation. Cultured primary human thyrocytes, from patients with and without GD, underwent CD40-stimulation. Once stimulated, cytokines and transcription factors specific for either the canonical NF-κB1 pathway (IL-6, IL-8, TNFα), which primarily recruits cells for innate immunity, or the noncanonical NF-κB2 pathway (BAFF, CCL21), which directs B cell viability, were analyzed. Significant upregulation in the mRNA and protei...