ArticlePloS one2013
Transiently reduced PI3K/Akt activity drives the development of regulatory function in antigen-stimulated Naïve T-cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- A regulatory circuit controlled by extranuclear and nuclear retinoic acid receptor α determines T cell activation and function.Immunity · 2023Article
- CounterAKTing HIV: Toward a "Block and Clear" Strategy?Frontiers in cellular and infection microbiology · 2022Review
- Regulatory T cells induced by B cells suppress NLRP3 inflammasome activation and alleviate monosodium urate-induced gouty inflammation.iScience · 2021Article
- Diverse Roles of Akt in T cells.Immunometabolism · 2021Article
- Control of T lymphocyte fate decisions by PI3K signaling.F1000Research · 2020Review
- Recent advances in regulatory T cells induced by B cells.Cellular & molecular immunology · 2018Article
- Naive CD4Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Regulatory T cells induced by B cells: a novel subpopulation of regulatory T cells.Journal of biomedical science · 2017Review
- Characterization of c-MafScientific reports · 2017Article
- The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment.Science advances · 2015Article
- Cannabidiol, a non-psychoactive cannabinoid, leads to EGR2-dependent anergy in activated encephalitogenic T cells.Journal of neuroinflammation · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T-cells (Tregs) are central for immune homeostasis and divided in thymus-derived natural Tregs and peripherally induced iTreg. However, while phenotype and function of iTregs are well known, a remarkable lack exists in knowledge about signaling mechanisms leading to their generation from naïve precursors in peripheral tissues. Using antigen specific naïve T-cells from mice, we investigated CD4+ CD25+ FoxP3- iTreg induction during antigen-specific T-cell receptor (TCR) stimulation with weak antigen presenting cells (APC). We show that early signaling pathways such as ADAM-17-activation appeared similar in developing iTreg and effector cells (Teff) and both initially shedded CD62-L. But iTreg started reexpressing CD62-L after 24 h while Teff permanently downmodulated it. Furthermore, between 24 and 72 hours iTreg presented with significantly lower phosphorylation levels of Akt-S473 suggesting lower activity of the PI3K/Akt-axis. This was associated with a higher expression of the Akt hydrophobic motif-specific phosphatase PHLPP1 in iTreg. Importantly, the lack of costimulatory signals via CD28 from weak APC was central for the development of regulatory function in iTreg but not for the reappearance of CD62-L. Thus, T-cells display a window of sensitivity after onset of TCR triggering within which the intensity of the PI3K/Akt signal controls entry into either effector or regulatory pathways.
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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.