Regulation of host immune responses by nuclear I.KAPPA.B proteins

Abstract

Nuclear factor-κB (NF-κB) plays an essential role in optimal activation of host immune systems, which isconserved from insects to mammals. Various microbial components and host-derived inflammatory cytokines activate NF-κB, leading to activation of the host immune system. Since excessive activation of NF-κB is harmful to the host, its activity is finely regulated at multiple steps in immune signaling pathways. One mechanism to prevent NF-κB activation is conducted by cytoplasmic IκB family proteins. Cytoplasmic IκBs have been shown to interact with NF-κB subunits in the cytoplasm of unstimulated cells. On stimulation, IκBs are rapidly degraded in a ubiquitin-proteasome dependent manner, allowing liberated NF-κB to translocate into the nucleus and activate the transcription of genes encoding various immune mediators. After the translocation of NF-κB from the cytoplasm to the nucleus, nuclear proteins structurally similar to cytoplasmic IκBs participate in the regulation of NF-κB activity as co-activators or -inhibitors through association with NF-κB subunits. For that reason, the regulatory IκB-like nuclear molecules are known as ‘nuclear IκB proteins’. In this review, we will discuss the physiological function of the nuclear IκB proteins, IκBξ, IκBNS, and Bcl-3 in the context of innate and adaptive immune responses.