ArticleCell death & disease2017
T-cell autonomous death induced by regeneration of inert glucocorticoid metabolites.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Targeting the glucocorticoid receptor-CCR8 axis mediated bone marrow T cell sequestration enhances infiltration of anti-tumor T cells in intracranial cancers.Cellular & molecular immunology · 2024Article
- Aire drives steroid hormone biosynthesis by medullary thymic epithelial cells.Science immunology · 2023Article
- Profiling of adrenal corticosteroids in blood and local tissues of mice during chronic stress.Scientific reports · 2023Article
- Glucocorticoid activation by HSD11B1 limits T cell-driven interferon signaling and response to PD-1 blockade in melanoma.Journal for immunotherapy of cancer · 2023Article
- Local glucocorticoid synthesis regulates house dust mite-induced airway hypersensitivity in mice.Frontiers in immunology · 2023Article
- Cell-Specific Immune Regulation by Glucocorticoids in Murine Models of Infection and Inflammation.Cells · 2022Review
- Discordance in STING-Induced Activation and Cell Death Between Mouse and Human Dendritic Cell Populations.Frontiers in immunology · 2022Article
- Revisiting steroidogenesis and its role in immune regulation with the advanced tools and technologies.Genes and immunity · 2021Review
- Dynamics of T Lymphocyte between the Periphery and the Brain from the Acute to the Chronic Phase Following Ischemic Stroke in Mice.Experimental neurobiology · 2021Article
- Glucocorticoids in T cell development, differentiation and function.Nature reviews. Immunology · 2021Review
- Early and Very Early GRIM19 and MCL1 Expression Are Correlated to Late Acquired Prednisolone Effects in a T-Cell Acute Leukemia Cell Line.Advances in experimental medicine and biology · 2021Article
- Role of Regulatory T Cells in Regulating Fetal-Maternal Immune Tolerance in Healthy Pregnancies and Reproductive Diseases.Frontiers in immunology · 2020Review
- Glucocorticoid Receptor-Deficient Foxp3Frontiers in immunology · 2019Article
- Cutting Edge: De Novo Glucocorticoid Synthesis by Thymic Epithelial Cells Regulates Antigen-Specific Thymocyte Selection.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Glucocorticoids (GC) are essential regulators of T-cell development and function. Activation of the immune system increases systemic adrenal-derived GC levels which downregulate immune activity as part of a negative feedback control system. Increasing evidence shows, however, that GC can also be derived from extra-adrenal sources such as the thymus or intestine, thus providing local control of GC-mediated effects. The thymus reportedly produces GC, but whether thymic epithelial cells or thymocytes produce GC acting either in an autocrine or paracrine fashion is not clear. We studied the expression of two main enzymes involved in de novo GC synthesis, CYP11A1 and CYP11B1, as well as the expression and activity of HSD11B1, an enzyme catalyzing interconversion of inert GC metabolites with active GC. While we found no evidence of de novo GC synthesis in both thymocytes and peripheral T cells, abundant regeneration of GC from the inactive metabolite 11-dehydrocorticosterone was detectable. Irrespective of their maturation stage, T cells that produced GC in this manner undergo autonomous cell death as this was blocked when glucocorticoid receptor-deficient T cells were treated with GC metabolites. These results indicate that both immature and mature T cells possess the capacity to undergo apoptosis in response to intrinsically generated GC. Consequently, positive selection of thymocytes, as well as survival of peripheral T cells may depend on TCR-induced escape of otherwise HSD11B1-driven autonomous T-cell death.
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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.