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

• Published in: The EMBO journal 2013-03, Vol.32 (6), p.816-828
• Main Authors: Mancino, Alessandra, Habbeddine, Mohamed, Johnson, Ella, Luron, Lionel, Bebien, Magali, Memet, Sylvie, Fong, Carol, Bajenoff, Marc, Wu, Xuefeng, Karin, Michael, Caamano, Jorge, Chi, Hongbo, Seed, Michael, Lawrence, Toby
• Format: Article
• Language: English
• Subjects: Adaptive Immunity - genetics; Adoptive Transfer - methods; Animals; Autoimmune diseases; Bacteria; Cell Differentiation - genetics; Cell Differentiation - immunology; Cells; Cells, Cultured; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - physiology; Dendritic Cells - transplantation; EMBO19; EMBO37; Humans; I kappa B Kinase alpha; I-kappa B Kinase - genetics; I-kappa B Kinase - metabolism; I-kappa B Kinase - physiology; Infections - genetics; Infections - immunology; Inflammation - genetics; Inflammation - immunology; interferon regulatory factor 3; Listeria monocytogenes; Listeria monocytogenes - immunology; Listeria monocytogenes - pathogenicity; Listeriosis - genetics; Listeriosis - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mycobacterium; Pathogens; T-cell priming; Tuberculosis; Vaccines
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2013.28

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 naïve T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKKα (CHUK) has previously been shown to have anti‐inflammatory activity and inhibit innate immunity. Here, we show that IKKα is required in DC for priming antigen‐specific T cells and acquired immunity to the human pathogen Listeria monocytogenes . We describe a new role for IKKα in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKKα 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. IKKα kinase has anti‐inflammatory activity. Here, IKKα is shown to be required in dendritic cells for T‐cell priming and acquired immunity to Listeria monocytogenes . IKKα thus inhibits the innate and activates the adaptive immune systems.