title: I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection.
abstract: 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.
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, Marseille, France.
authors: Alessandra
authors: A
authors: Mancino
authors: Mohamed
authors: M
authors: Habbeddine
authors: Ella
authors: E
authors: Johnson
authors: Lionel
authors: L
authors: Luron
authors: Magali
authors: M
authors: Bebien
authors: Sylvie
authors: S
authors: Memet
authors: Carol
authors: C
authors: Fong
authors: Marc
authors: M
authors: Bajenoff
authors: Xuefeng
authors: X
authors: Wu
authors: Michael
authors: M
authors: Karin
authors: Jorge
authors: J
authors: Caamano
authors: Hongbo
authors: H
authors: Chi
authors: Michael
authors: M
authors: Seed
authors: Toby
authors: T
authors: Lawrence
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007239:Infections / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology / Q000472:pathogenicity; D008088:Listeriosis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D051550:I-kappa B Kinase