ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Protein kinase C-θ inhibits inducible regulatory T cell differentiation via an AKT-Foxo1/3a-dependent pathway.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- TDRD3, a Tudor domain-containing protein, regulatesScience advances · 2026Article
- Gut microbiota depletion accelerates hematoma resolution and neurological recovery after intracerebral hemorrhage via p-coumaric acid-promoted Treg differentiation.Theranostics · 2025Article
- Proteome characterization of extracellular vesicles from human milk: Uncovering the surfaceome by a lipid-based protein immobilization technology.Journal of extracellular biology · 2024Article
- Cancer-associated SF3B1-K700E mutation controls immune responses by regulating TScience advances · 2024Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Steroid nuclear receptor coactivator 2 controls immune tolerance by promoting induced TScience advances · 2022Article
- The role of metabolism on regulatory T cell development and its impact in tumor and transplantation immunity.Frontiers in immunology · 2022Review
- Akt isoforms in the immune system.Frontiers in immunology · 2022Review
- NKD2 mediates stimulation-dependent ORAI1 trafficking to augment CaCell reports · 2021Article
- Signal Transduction in Immune Cells and Protein Kinases.Advances in experimental medicine and biology · 2021Article
- Diverse Roles of Akt in T cells.Immunometabolism · 2021Article
- Tuning T helper cell differentiation by ITK.Biochemical Society transactions · 2020Review
- The vimentin intermediate filament network restrains regulatory T cell suppression of graft-versus-host disease.The Journal of clinical investigation · 2018Article
- SRC1 promotes Th17 differentiation by overriding Foxp3 suppression to stimulate RORγt activity in a PKC-θ-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Mild hypothermia pretreatment protects against liver ischemia reperfusion injury via the PI3K/AKT/FOXO3a pathway.Molecular medicine reports · 2017Article
- Pharmacological Inhibition of PKCθ Counteracts Muscle Disease in a Mouse Model of Duchenne Muscular Dystrophy.EBioMedicine · 2017Article
- Protein kinase C theta is dispensable for suppression mediated by CD25+CD4+ regulatory T cells.PloS one · 2017Article
- Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response.Archivum immunologiae et therapiae experimentalis · 2016Article
- Tumor Progression Locus 2 (Tpl2) Activates the Mammalian Target of Rapamycin (mTOR) Pathway, Inhibits Forkhead Box P3 (FoxP3) Expression, and Limits Regulatory T Cell (Treg) Immunosuppressive Functions.The Journal of biological chemistry · 2016Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Protein kinase C (PKC)-θ has been shown to be a critical TCR signaling molecule that promotes the activation and differentiation of naive T cells into inflammatory effector T cells. In this study, we demonstrate that PKC-θ-mediated signals inhibit inducible regulatory T cell (iTreg) differentiation via an AKT-Foxo1/3A pathway. TGF-β-induced iTreg differentiation was enhanced in PKC-θ(-/-) T cells or wild-type cells treated with a specific PKC-θ inhibitor, but was inhibited by the PKC-θ activator PMA, or by CD28 crosslinking, which enhances PKC-θ activation. PKC-θ(-/-) T cells had reduced activity of the AKT kinase, and the expression of a constitutively active form of AKT in PKC-θ(-/-) T cells restored the ability to inhibit iTreg differentiation. Furthermore, knockdown or overexpression of the AKT downstream targets Foxo1 and Foxo3a was found to inhibit or promote iTreg differentiation in PKC-θ(-/-) T cells accordingly, indicating that the AKT-Foxo1/3A pathway is responsible for the inhibition of iTreg differentiation of iTregs downstream of PKC-θ. We conclude that PKC-θ is able to control T cell-mediated immune responses by shifting the balance between the differentiation of effector T cells and inhibitory Tregs.
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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.