ArticleProceedings of the National Academy of Sciences of the United States of America2019
Medullary thymic epithelial NF-kB-inducing kinase (NIK)/IKKα pathway shapes autoimmunity and liver and lung homeostasis in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- The NF-κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets.Journal of cellular and molecular medicine · 2026Review
- Runx3 instructs AireJournal of autoimmunity · 2026Article
- Human inborn errors of the alternative NF-κB pathway.Journal of human immunity · 2026Review
- Biliary NF-κB-Inducing Kinase Promotes Ductular Reaction, Inflammation, and Fibrosis and Impedes Liver Disease Resolution.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- An iPSC-based in vitro model recapitulates human thymic epithelial development and multi-lineage specification.Nature communications · 2025Article
- Double trouble: cytosolic and nuclear IKKα in cancer.Open biology · 2025Review
- NF-κB in inflammation and cancer.Cellular & molecular immunology · 2025Review
- NF-κB: master regulator of cellular responses in health and disease.Immunity & inflammation · 2025Review
- Long-term outcome of bone marrow transplantation in NIK deficiency: non-redundant role of non-canonical NF-κB signaling in thymic reconstitution and secondary lymphoid organ development.Frontiers in immunology · 2025Article
- The Proteostasis of Thymic Stromal Cells in Health and Diseases.The protein journal · 2024Review
- Comprehensive Transcriptomic Analysis for Thymic Epithelial Cells of Aged Mice and Humans.Immune network · 2023Article
- Biliary NIK promotes ductular reaction and liver injury and fibrosis in mice.Nature communications · 2022Article
- Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis.Annual review of nutrition · 2022Review
- Transcriptomic diversity in human medullary thymic epithelial cells.Nature communications · 2022Article
- Progress and Prospects of Non-Canonical NF-κB Signaling Pathway in the Regulation of Liver Diseases.Molecules (Basel, Switzerland) · 2022Review
- Thymocytes trigger self-antigen-controlling pathways in immature medullary thymic epithelial stages.eLife · 2022Article
- Cytosolic Nuclear Sensor Dhx9 Controls Medullary Thymic Epithelial Cell Differentiation by p53-Mediated Pathways.Frontiers in immunology · 2022Article
- NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells.Molecular medicine reports · 2021Article
- Dual roles for LUBAC signaling in thymic epithelial cell development and survival.Cell death and differentiation · 2021Article
- Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα).Science immunology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Aberrant T cell development is a pivotal risk factor for autoimmune disease; however, the underlying molecular mechanism of T cell overactivation is poorly understood. Here, we identified NF-κB-inducing kinase (NIK) and IkB kinase α (IKKα) in thymic epithelial cells (TECs) as essential regulators of T cell development. Mouse TEC-specific ablation of either NIK or IKKα resulted in severe T cell-mediated inflammation, injury, and fibrosis in the liver and lung, leading to premature death within 18 d of age. NIK or IKKα deficiency abrogated medullary TEC development, and led to breakdown of central tolerance, production of autoreactive T cells, and fatal autoimmune destruction in the liver and lung. TEC-specific ablation of NIK or IKKα also impaired thymic T cell development from the double-negative through the double-positive stages and inhibited peripheral B cell development. These results unravel a hitherto unrecognized essential role of TEC-intrinsic NIK and IKKα pathways in autoimmunity and T cell-instigated chronic liver and lung diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.