ArticleProceedings of the National Academy of Sciences of the United States of America2014
Ndfip1 mediates peripheral tolerance to self and exogenous antigen by inducing cell cycle exit in responding CD4+ T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Adaptor-mediated interaction between Kv1.3 and Nedd4-2 E3 ubiquitin ligase.Communications biology · 2026Article
- Tonsillar expression quantitative trait loci verify and expand genetic contributors to childhood atopic diseases.bioRxiv : the preprint server for biology · 2026Article
- RAG suppresses group 2 innate lymphoid cells.eLife · 2025Article
- Cabergoline-induced NDFIP1 upregulation in pituitary neuroendocrine tumor cells activates mTOR signaling and contributes to cabergoline resistance.Journal of neuro-oncology · 2025Article
- Functional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts.American journal of human genetics · 2025Article
- The CD8Immunity · 2024Article
- Investigating shared genetic architecture between inflammatory bowel diseases and primary biliary cholangitis.JHEP reports : innovation in hepatology · 2024Article
- SLIDE: Significant Latent Factor Interaction Discovery and Exploration across biological domains.Nature methods · 2024Article
- Identifying disease-critical cell types and cellular processes by integrating single-cell RNA-sequencing and human genetics.Nature genetics · 2022Article
- Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients.Scientific reports · 2021Article
- The Ubiquitin Ligase Adaptor NDFIP1 Selectively Enforces a CD8Cell reports · 2018Article
- Ndfip1 restricts mTORC1 signalling and glycolysis in regulatory T cells to prevent autoinflammatory disease.Nature communications · 2017Article
- Ndfip1 restricts Th17 cell potency by limiting lineage stability and proinflammatory cytokine production.Scientific reports · 2017Article
- The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation.Nature communications · 2016Article
- Blood and Intestine eQTLs from an Anti-TNF-Resistant Crohn's Disease Cohort Inform IBD Genetic Association Loci.Clinical and translational gastroenterology · 2016Article
- Ndfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4+ effector T cells.Nature communications · 2016Article
- iGWAS: Integrative Genome-Wide Association Studies of Genetic and Genomic Data for Disease Susceptibility Using Mediation Analysis.Genetic epidemiology · 2015Article
- Does antigen masking by ubiquitin chains protect from the development of autoimmune diseases?Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The NDFIP1 (neural precursor cell expressed, developmentally down-regulated protein 4 family-interacting protein 1) adapter for the ubiquitin ligase ITCH is genetically linked to human allergic and autoimmune disease, but the cellular mechanism by which these proteins enable foreign and self-antigens to be tolerated is unresolved. Here, we use two unique mouse strains--an Ndfip1-YFP reporter and an Ndfip1-deficient strain--to show that Ndfip1 is progressively induced during T-cell differentiation and activation in vivo and that its deficiency causes a cell-autonomous, Forkhead box P3-independent failure of peripheral CD4(+) T-cell tolerance to self and exogenous antigen. In small cohorts of antigen-specific CD4(+) cells responding in vivo, Ndfip1 was necessary for tolerogen-reactive T cells to exit cell cycle after one to five divisions and to abort Th2 effector differentiation, defining a step in peripheral tolerance that provides insights into the phenomenon of T-cell anergy in vivo and is distinct from the better understood process of Bcl2-interacting mediator of cell death-mediated apoptosis. Ndfip1 deficiency precipitated autoimmune pancreatic destruction and diabetes; however, this depended on a further accumulation of nontolerant anti-self T cells from strong stimulation by exogenous tolerogen. These findings illuminate a peripheral tolerance checkpoint that aborts T-cell clonal expansion against allergens and autoantigens and demonstrate how hypersensitive responses to environmental antigens may trigger autoimmunity.
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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.