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

Alessandra Mancino, Mohamed Habbeddine, Ella Johnson, Lionel Luron, Magali Bebien, Sylvie Memet, Carol Fong, Marc Bajenoff, Xuefeng Wu, Michael Karin, Jorge Caamano, Hongbo Chi, Michael Seed, Toby Lawrence

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)816-28
Number of pages13
JournalThe EMBO journal
Volume32
Issue number6
DOIs
Publication statusPublished - 20 Mar 2013

Keywords

  • Adaptive Immunity/genetics
  • Adoptive Transfer/methods
  • Animals
  • Cell Differentiation/genetics
  • Cells, Cultured
  • Dendritic Cells/immunology
  • Humans
  • I-kappa B Kinase/genetics
  • Infection/genetics
  • Inflammation/genetics
  • Listeria monocytogenes/immunology
  • Listeriosis/genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic

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