ArticleJournal of immunology (Baltimore, Md. : 1950)2015
mTORC2 Deficiency in Myeloid Dendritic Cells Enhances Their Allogeneic Th1 and Th17 Stimulatory Ability after TLR4 Ligation In Vitro and In Vivo.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- The role of mTORC2/RICTOR in immune cells and inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Advances in dendritic cell targeting nano-delivery systems for induction of immune tolerance.Frontiers in bioengineering and biotechnology · 2023Review
- Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin.Frontiers in aging neuroscience · 2022Article
- mTORC2 confers neuroprotection and potentiates immunity during virus infection.Nature communications · 2021Article
- The role of RICTOR amplification in targeted therapy and drug resistance.Molecular medicine (Cambridge, Mass.) · 2020Review
- Regulation of RLR-Mediated Antiviral Responses of Human Dendritic Cells by mTOR.Frontiers in immunology · 2020Article
- Response of metastatic mouse invasive lobular carcinoma to mTOR inhibition is partly mediated by the adaptive immune system.Oncoimmunology · 2020Article
- Inactivation of mTORC2 in macrophages is a signature of colorectal cancer that promotes tumorigenesis.JCI insight · 2019Article
- DNAX Activating Protein of 12 kDa/Triggering Receptor Expressed on Myeloid Cells 2 Expression by Mouse and Human Liver Dendritic Cells: Functional Implications and Regulation of Liver Ischemia-Reperfusion Injury.Hepatology (Baltimore, Md.) · 2019Article
- The "other" mTOR complex: New insights into mTORC2 immunobiology and their implications.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Review
- LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity.Cell research · 2019Article
- mTORC2 deficiency in cutaneous dendritic cells potentiates CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- mTORC2 Deficiency Alters the Metabolic Profile of Conventional Dendritic Cells.Frontiers in immunology · 2019Article
- Rictor deficiency in dendritic cells exacerbates acute kidney injury.Kidney international · 2018Article
- Production of interleukin-1β related to mammalian target of rapamycin/Toll-like receptor 4 signaling pathway duringInternational journal of ophthalmology · 2018Article
- Regulation of Dendritic Cell Immune Function and Metabolism by Cellular Nutrient Sensor Mammalian Target of Rapamycin (mTOR).Frontiers in immunology · 2018Review
- Influence of the Novel ATP-Competitive Dual mTORC1/2 Inhibitor AZD2014 on Immune Cell Populations and Heart Allograft Rejection.Transplantation · 2017Article
- Suppression of Th17-polarized airway inflammation by rapamycin.Scientific reports · 2017Article
- MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.Immunity · 2017Review
- Innate Immune Regulations and Liver Ischemia-Reperfusion Injury.Transplantation · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian/mechanistic target of rapamycin (mTOR) is a key integrative kinase that functions in two independent complexes, mTOR complex (mTORC) 1 and mTORC2. In contrast to the well-defined role of mTORC1 in dendritic cells (DC), little is known about the function of mTORC2. In this study, to our knowledge, we demonstrate for the first time an enhanced ability of mTORC2-deficient myeloid DC to stimulate and polarize allogeneic T cells. We show that activated bone marrow-derived DC from conditional Rictor(-/-) mice exhibit lower coinhibitory B7-H1 molecule expression independently of the stimulus and enhanced IL-6, TNF-α, IL-12p70, and IL-23 production following TLR4 ligation. Accordingly, TLR4-activated Rictor(-/-) DC display augmented allogeneic T cell stimulatory ability, expanding IFN-γ(+) and IL-17(+), but not IL-10(+) or CD4(+)Foxp3(+) regulatory T cells in vitro. A similar DC profile was obtained by stimulating Dectin-1 (C-type lectin family member) on Rictor(-/-) DC. Using novel CD11c-specific Rictor(-/-) mice, we confirm the alloreactive Th1 and Th17 cell-polarizing ability of endogenous mTORC2-deficient DC after TLR4 ligation in vivo. Furthermore, we demonstrate that proinflammatory cytokines produced by Rictor(-/-) DC after LPS stimulation are key in promoting Th1/Th17 responses. These data establish that mTORC2 activity restrains conventional DC proinflammatory capacity and their ability to polarize T cells following TLR and non-TLR stimulation. Our findings provide new insight into the role of mTORC2 in regulating DC function and may have implications for emerging therapeutic strategies that target mTOR in cancer, infectious diseases, and transplantation.
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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.