Miraghazadeh, BaharCook, Matthew2021-11-182021-11-181664-3224http://hdl.handle.net/1885/251895NF-κB (nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-κB 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-κB signaling and regulation, then summarize important molecular contributions of NF-κB 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-κB pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-κB mutations, and speculate on implications for understanding sporadic autoimmune disease.This work was supported by NHMRC program grant 1113577, NHMRC project grant 1079648, and NHMRC Centre of Research Excellence grant 1107464.application/pdfen-AUCopyright © 2018 Miraghazadeh and Cook.https://creativecommons.org/licenses/by/4.0/NF-κBautoimmunityself-tolerancethymic developmentmutation201810.3389/fimmu.2018.006132020-11-23Creative Commons Attribution License (CC BY)