Human inborn errors of the alternative NF-κB pathway
Year: 2025
Type: article
Abstract: Inborn errors of the "core" components of the alternative NF-κB pathway-NIK, IKK-α, RelB, and NF-κB2-underlie various T and/or B cell deficiencies, frequently associated with syndromic features, including ectodermal dysplasia and lymph node hypoplasia. Their impact on medullary thymic stromal cells (mTECs) also underlies the development of autoantibodies neutralizing type I interferons (IFNs), conferring a predisposition to severe viral diseases. Inborn errors of "upstream" ligands or surface receptors engaging this pathway affect secondary lymphoid organ organization (LTβR), B cell development and survival (BAFFR), T cell and antigen-presenting cell costimulation (CD40L/CD40), or osteoclast differentiation (RANK/RANKL). Finally, inborn errors of TRAF3, a negative "regulator" of this pathway, underlie immune dysregulation, infection, and lymphoproliferation. Various inborn errors of the human alternative NF-κB pathway have, thus, delineated the essential and redundant roles of its components in leukocytic and non-leukocytic cells.
Source: Journal of Human Immunity
Authors: Tom Le Voyer, Jean-Laurent Casanova, Anne Puel
Language: English
Topic: NF-κB Signaling Pathways
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
Awards: Autoantibodies against Interferons underlying Infectious Diseases, Genetic predisposition and anti-IFN autoantibodies underlying severe influenza., Autoantibodies against type I IFNs in Lebanese patients hospitalized with COVID-19., Institut Hospitalo-Universitaire Imagine, Integrative Biology of Emerging Infectious Diseases, Multi-omic analysis of anti-viral immunity: From the identification of relevant biological pathways to the discovery of inborn errors of immunity, Covid-19 and interferons: from discovery to therapy, Genome-wide search for inborn errors of IL-17 immunity underlying chronic mucocutaneous candidiasis, Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational Success, Inborn errors of immunity in patients with life-threatening COVID-19
OpenAlex ID: W4416504082