ArticleThe Journal of clinical investigation2014
iNKT cells require TSC1 for terminal maturation and effector lineage fate decisions.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 56 citations in OpenAlex.
- Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics.Molecular psychiatry · 2026Article
- CD23 sustains NKT17 cell homeostasis via IL-7Rα-mTORC2 signaling.Cell death & disease · 2026Article
- FNIP1 Modulates B Cell Receptor Signaling Strength by Coordinating Metabolism During Development.bioRxiv : the preprint server for biology · 2026Article
- Progranulin regulates the development and function of NKT2 cells through EZH2 and PLZF.Cell death and differentiation · 2022Article
- Obesity-Mediated Immune Modulation: One Step Forward, (Th)2 Steps Back.Frontiers in immunology · 2022Review
- Role of TSC1 in physiology and diseases.Molecular and cellular biochemistry · 2021Review
- Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.Nature communications · 2021Article
- Thymic Epithelial Cell-Derived IL-15 and IL-15 Receptor α Chain Foster Local Environment for Type 1 Innate Like T Cell Development.Frontiers in immunology · 2021Article
- Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.European journal of immunology · 2020Article
- Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-γ in NK cells.The Journal of clinical investigation · 2020Article
- Hippo/Mst signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions.The Journal of experimental medicine · 2020Article
- mTOR signaling at the crossroads of environmental signals and T-cell fate decisions.Immunological reviews · 2020Review
- Mammalian Target of Rapamycin Signaling Enhances Ovalbumin-Induced Neutrophilic Airway Inflammation by Promoting Th17 Cell Polarization in Murine Noneosinophilic Asthma Model.Pediatric allergy, immunology, and pulmonology · 2020Article
- Graded diacylglycerol kinases α and ζ activities ensure mucosal-associated invariant T-cell development in mice.European journal of immunology · 2020Article
- Metabolic coordination of T cell quiescence and activation.Nature reviews. Immunology · 2020Review
- PDCD5 regulates iNKT cell terminal maturation and iNKT1 fate decision.Cellular & molecular immunology · 2019Article
- Differential Control ofFrontiers in immunology · 2019Article
- Raptor/mTORC1 Acts as a Modulatory Center to Regulate Anti-bacterial Immune Response in Rockfish.Frontiers in immunology · 2019Article
- Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23.Nature communications · 2018Article
- The Role of Autophagy in iNKT Cell Development.Frontiers in immunology · 2018Review
Corrections and comments
- Erratum issued
- Expression of concern
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Terminal maturation of invariant NKT (iNKT) cells from stage 2 (CD44+NK1.1-) to stage 3 (CD44+NK1.1+) is accompanied by a functional acquisition of a predominant IFN-γ-producing (iNKT-1) phenotype; however, some cells develop into IL-17-producing iNKT (iNKT-17) cells. iNKT-17 cells are rare and restricted to a CD44+NK1.1- lineage. It is unclear how iNKT terminal maturation is regulated and what factors mediate the predominance of iNKT-1 compared with iNKT-17. The tumor suppressor tuberous sclerosis 1 (TSC1) is an important negative regulator of mTOR signaling, which regulates T cell differentiation, function, and trafficking. Here, we determined that mice lacking TSC1 exhibit a developmental block of iNKT differentiation at stage 2 and skew from a predominantly iNKT-1 population toward a predominantly iNKT-17 population, leading to enhanced airway hypersensitivity. Evaluation of purified iNKT cells revealed that TSC1 promotes T-bet, which regulates iNKT maturation, but downregulates ICOS expression in iNKT cells by inhibiting mTOR complex 1 (mTORC1). Furthermore, mice lacking T-bet exhibited both a terminal maturation defect of iNKT cells and a predominance of iNKT-17 cells, and increased ICOS expression was required for the predominance of iNKT-17 cells in the population of TSC1-deficient iNKT cells. Our data indicate that TSC1-dependent control of mTORC1 is crucial for terminal iNKT maturation and effector lineage decisions, resulting in the predominance of iNKT-1 cells.
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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.