I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection

Dendritic cells (DC) are required for priming antigen-specific T cells and acquired immunity to many important human pathogens, including Mycobacteriuim tuberculosis (TB) and influenza. However, inappropriate priming of auto-reactive T cells is linked with autoimmune disease. Understanding the molecular mechanisms that regulate the priming and activation of naive T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKK alpha (CHUK) has previously been shown to have anti-inflammatory activity and inhibit innate immunity. Here, we show that IKK alpha is required in DC for priming antigen-specific Tcells and acquired immunity to the human pathogen Listeria monocytogenes. We describe a new role for IKK alpha in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKK alpha in dampening inflammation while simultaneously promoting adaptive immunity that could have important implications for the development of new vaccine adjuvants and treatment of autoimmune diseases. The EMBO Journal (2013) 32, 816-828. doi:10.1038/emboj.2013.28; Published online 19 February 2013