Nuclear Factor-kappaB in Autoimmunity: Man and Mouse

NF-kappa B nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-kappa B signaling, mediated by nuclear translocation of RelA, c-Rel, and p50, is important for immune cell activation, differentiation, and survival. Non-canonical signaling mediated by nuclear translocation of p52 and RelB contributes to lymphocyte maturation and survival and is also crucial for lymphoid organogenesis. We outline NF-kappa B signaling and regulation, then summarize important molecular contributions of NF-kappa B to mechanisms of self-tolerance. We relate these mechanisms to autoimmune phenotypes described in what is now a substantial catalog of immune defects conferred by mutations in NF-kappa B pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-kappa B mutations, and speculate on implications for understanding sporadic autoimmune disease.