Turning NF-kappaB and IRFs on and off in DC.
Dendritic cells (DCs) produce an array of cytokines after detecting various immune adjuvants through pattern recognition receptors (PRRs). PRR signaling leads to activation of transcription factors such as NF-kappaB or interferon regulatory factors (IRFs) but after activation must be attenuated to avoid immunopathology and to maintain tissue homeostasis. IkappaB kinase family members, originally identified as classical NF-kappaB activators, are now found to be broadly and crucially involved in PRR signaling in a member-specific manner. Furthermore, a new mechanism for NF-kappaB downregulation is emerging that involves the degradation of active NF-kappaB by the nuclear ubiquitin-proteasome system. Here we review new aspects of NF-kappaB and IRF regulation chiefly in DCs.
Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama city, Kanagawa 230-0045, Japan. tkaisho@rcai.riken.jp
Tsuneyasu
T
Kaisho
Takashi
T
Tanaka
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D050838:Interferon Regulatory Factor-3 / Q000502:physiology*; D050839:Interferon Regulatory Factor-7 / Q000502:physiology*; D007370:Interferon Type I / Q000096:biosynthesis; D016328:NF-kappa B / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D051199:Toll-Like Receptor 7 / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000502:physiology
D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D016328:NF-kappa B; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase