ArticleThe Journal of clinical investigation2012
Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 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
81 citing papers in PubMed, 131 citations in OpenAlex.
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- Selective Glucocorticoid Receptor Modulators of Immune Checkpoint Function.bioRxiv : the preprint server for biology · 2026Article
- Mechanical Insights into the Distinct Effects of Ovariectomy Versus Adrenalectomy on Age-Related Thymic Atrophy in Female Mice.International journal of molecular sciences · 2026Article
- Neuroepithelial VIP-VIPR1 interactions differentially control enteric type 1 and type 2 immunity.Nature immunology · 2025Article
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- Hypoxia inducible factor 1α-driven steroidogenesis impacts systemic hematopoiesis.Cellular & molecular biology letters · 2025Article
- Peripheral CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
- 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
- Endogenous glucocorticoids are required for normal macrophage activation and gastricAmerican journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment.Cancer cell · 2024Article
- Primary and secondary defects of the thymus.Immunological reviews · 2024Review
- Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction.Frontiers in endocrinology · 2024Article
- Mini-TCRs: Truncated T cell receptors to generate T cells from induced pluripotent stem cells.Molecular therapy. Methods & clinical development · 2023Article
- Tumors produce glucocorticoids by metabolite recycling, not synthesis, and activate Tregs to promote growth.The Journal of clinical investigation · 2023Article
- Aire drives steroid hormone biosynthesis by medullary thymic epithelial cells.Science immunology · 2023Article
- Adolescent stress impairs postpartum social behavior via anterior insula-prelimbic pathway in mice.Nature communications · 2023Article
- Adolescent stress impairs postpartum social behavior via anterior insula-prelimbic pathway.bioRxiv : the preprint server for biology · 2023Article
- Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids.Molecular metabolism · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Generation of a self-tolerant but antigen-responsive T cell repertoire occurs in the thymus. Although glucocorticoids are usually considered immunosuppressive, there is also evidence that they play a positive role in thymocyte selection. To address the question of how endogenous glucocorticoids might influence the adaptive immune response, we generated GRlck-Cre mice, in which the glucocorticoid receptor gene (GR) is deleted in thymocytes prior to selection. These mice were immunocompromised, with reduced polyclonal T cell proliferative responses to alloantigen, defined peptide antigens, and viral infection. This was not due to an intrinsic proliferation defect, because GR-deficient T cells responded normally when the TCR was cross-linked with antibodies or when the T cell repertoire was "fixed" with αβ TCR transgenes. Varying the affinity of self ligands in αβ TCR transgenic mice showed that affinities that would normally lead to thymocyte-positive selection caused negative selection, and alterations in the TCR repertoire of polyclonal T cells were confirmed by analysis of TCR Vβ CDR3 regions. Thus, endogenous glucocorticoids are required for a robust adaptive immune response because of their promotion of the selection of T cells that have sufficient affinity for self, and the absence of thymocyte glucocorticoid signaling results in an immunocompromised state.
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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.