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.