ArticleJournal of immunology (Baltimore, Md. : 1950)2013
T cell activation threshold regulated by E3 ubiquitin ligase Cbl-b determines fate of inducible regulatory T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- A high dimensionality approach reveals immunopathogenic responses driving severe pediatric acute respiratory distress syndrome.Nature communications · 2026Article
- Integrative Transcriptomics Identifies Ubiquitination-Related GenesJournal of inflammation research · 2026Article
- K27-linked RORγt ubiquitination by Nedd4 potentiates Th17-mediated autoimmunity.Journal of biomedical science · 2025Article
- Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions.Life (Basel, Switzerland) · 2024Review
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Mechanism study of ubiquitination in T cell development and autoimmune disease.Frontiers in immunology · 2024Review
- The Function of Ubiquitination in T-Cell Development.Advances in experimental medicine and biology · 2024Review
- Integrated Bioinformatics Analysis for Revealing CBL is a Potential Diagnosing Biomarker and Related Immune Infiltration in Parkinson's Disease.International journal of general medicine · 2024Article
- Classification and deep-learning-based prediction of Alzheimer disease subtypes by using genomic data.Translational psychiatry · 2023Article
- Targeting Cbl-b in cancer immunotherapy.Journal for immunotherapy of cancer · 2023Review
- Akt-2 Is a Potential Therapeutic Target for Disseminated Candidiasis.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.Clinical and experimental immunology · 2021Review
- Diverse Roles of Akt in T cells.Immunometabolism · 2021Article
- Chromatin Priming Renders T Cell Tolerance-Associated Genes Sensitive to Activation below the Signaling Threshold for Immune Response Genes.Cell reports · 2020Article
- Sequential ubiquitination of NLRP3 by RNF125 and Cbl-b limits inflammasome activation and endotoxemia.The Journal of experimental medicine · 2020Article
- Regulation of immune responses by E3 ubiquitin ligase Cbl-b.Cellular immunology · 2019Review
- The E3 ligase Hrd1 stabilizes Tregs by antagonizing inflammatory cytokine-induced ER stress response.JCI insight · 2019Article
- Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Chronic Constriction Injury.Neurochemical research · 2018Article
- mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3Journal of immunology (Baltimore, Md. : 1950) · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-b (Cbl-b) is critical for establishing the threshold for T cell activation and is essential for induction of T cell anergy. Recent studies suggest that Cbl-b is involved in the development of CD4(+)CD25(+) inducible regulatory T cells (iTregs). In this study, we report that the optimal induction of Foxp3 by naive CD4(+)CD25(-) T cells requires suboptimal TCR triggering. In the absence of Cbl-b, the TCR strength for optimal Foxp3 induction is downregulated in vitro. Using TCR-transgenic Rag(-/-) mice in combination with Cbl-b deficiency, we show that in vivo iTreg development is also controlled by Cbl-b via tuning the TCR strength. Furthermore, we show that Akt-2 but not Akt-1 regulates Foxp3 expression downstream of Cbl-b. Therefore, we demonstrate that Cbl-b regulates the fate of iTregs via controlling the threshold for T cell activation.
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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.