Mistuned NF-κB signaling in lymphocytes: lessons from relevant inborn errors of immunity

Inborn errors of immunity (IEIs) continuously remind us that multiple checks and balances are built into the adaptive immune system to maintain homeostasis, ensuring effective pathogen defense without causing inadvertent immunopathology, autoimmunity, or lymphomagenesis. The nuclear factor of kappa B (NF-kappa B) family of transcription factors serve a vital role in the immune system, inducing scores of genes responsible for lymphocyte survival, proliferation, differentiation and effector function. In recent years, the discovery and characterization of IEIs that impact NF-kappa B activity have illuminated the importance of carefully tuning this pathway to ensure effective immune defense without hyperinflammation and immune dysregulation. Here we examine several illustrative cases of IEIs that arise from pathogenic mutations encoding NF-kappa B inducers, regulators, and NF-kappa B family components themselves, illuminating how these genes ensure normal adaptive immune system function by maintaining a Goldilocks effect state in NF-kappa B pathway activity.

Automated summary

Inborn errors of immunity (IEIs) emphasize the importance of maintaining a balanced immune system to effectively defend against pathogens without causing immunopathology. The nuclear factor of kappa B (NF-kappa B) family of transcription factors play a crucial role in the immune system by regulating genes responsible for lymphocyte function. Recent research on IEIs impacting NF-kappa B activity highlights the need to carefully regulate this pathway to prevent hyperinflammation and immune dysregulation. This article examines specific cases of IEIs caused by mutations in NF-kappa B inducers, regulators, and components, illustrating how these genes maintain an optimal state of NF-kappa B pathway activity for normal adaptive immune system function.