Turning NF-κB 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-kappa B or interferon regulatory factors (IRFs) but after activation must be attenuated to avoid immunopathology and to maintain tissue homeostasis. I kappa B kinase family members, originally identified as classical NF-kappa B activators, are now found to be broadly and crucially involved in PRR signaling in a member-specific manner. Furthermore, a new mechanism for NF-kappa B downregulation is emerging that involves the degradation of active NF-kappa B by the nuclear ubiquitin-proteasome system. Here we review new aspects of NF-kappa B and IRF regulation chiefly in DCs.