ArticleProceedings of the National Academy of Sciences of the United States of America2015
Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Low-dose IL-2 improved clinical symptoms by restoring reduced regulatory T cells in patients with refractory rheumatoid arthritis: A randomized controlled trial.Frontiers in immunology · 2022Trial
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Mechanism of tacrolimus in the treatment of lupus nephritis.Frontiers in pharmacology · 2024Review
- Review
- Bioinformatic analysis and experimental validation of the potential gene in the airway inflammation of steroid-resistant asthma.Scientific reports · 2023Article
- Novel Biomarkers for Diagnosis and Monitoring of Immune Thrombocytopenia.International journal of molecular sciences · 2023Review
- Targeting the Adaptive Immune System in Depression: Focus on T Helper 17 Cells.Pharmacological reviews · 2022Review
- Supra-lacrimal protein-based carriers for cyclosporine A reduce Th17-mediated autoimmunity in murine model of Sjögren's syndrome.Biomaterials · 2022Article
- Panax notoginseng saponins reverse P-gp-mediated steroid resistance in lupus: involvement in the suppression of the SIRT1/FoxO1/MDR1 signalling pathway in lymphocytes.BMC complementary medicine and therapies · 2022Article
- Coadministration of Stigmasterol and Dexamethasone (STIG+DEX) Modulates Steroid-Resistant Asthma.Mediators of inflammation · 2022Article
- Effect of systemic steroid therapy in Graves' orbitopathy on regulatory T cells and Th17/Treg ratio.Journal of endocrinological investigation · 2021Article
- CD4International journal of molecular sciences · 2021Review
- Glucocorticoids in T cell development, differentiation and function.Nature reviews. Immunology · 2021Review
- Control of immunity by glucocorticoids in health and disease.Seminars in immunopathology · 2020Review
- Role of Multidrug Resistance Proteins in Nonresponders to Immunomodulatory Therapy for Noninfectious Uveitis.Translational vision science & technology · 2020Article
- Targeting the phosphorylation site of myristoylated alanine-rich C kinase substrate alleviates symptoms in a murine model of steroid-resistant asthma.British journal of pharmacology · 2019Article
- High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Clinical Remission of Sight-Threatening Non-Infectious Uveitis Is Characterized by an Upregulation of Peripheral T-Regulatory Cell Polarized Towards T-bet and TIGIT.Frontiers in immunology · 2018Article
- High-Dimensional Profiling Reveals Heterogeneity of the Th17 Subset and Its Association With Systemic Immunomodulatory Treatment in Non-infectious Uveitis.Frontiers in immunology · 2018Article
- Regulatory and Mechanistic Actions of Glucocorticoids on T and Inflammatory Cells.Frontiers in endocrinology · 2018Review
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
Glucocorticoids remain the cornerstone of treatment for inflammatory conditions, but their utility is limited by a plethora of side effects. One of the key goals of immunotherapy across medical disciplines is to minimize patients' glucocorticoid use. Increasing evidence suggests that variations in the adaptive immune response play a critical role in defining the dose of glucocorticoids required to control an individual's disease, and Th17 cells are strong candidate drivers for nonresponsiveness [also called steroid resistance (SR)]. Here we use gene-expression profiling to further characterize the SR phenotype in T cells and show that Th17 cells generated from both SR and steroid-sensitive individuals exhibit restricted genome-wide responses to glucocorticoids in vitro, and that this is independent of glucocorticoid receptor translocation or isoform expression. In addition, we demonstrate, both in transgenic murine T cells in vitro and in an in vivo murine model of autoimmunity, that Th17 cells are reciprocally sensitive to suppression with the calcineurin inhibitor, cyclosporine A. This result was replicated in human Th17 cells in vitro, which were found to have a conversely large genome-wide shift in response to cyclosporine A. These observations suggest that the clinical efficacy of cyclosporine A in the treatment of SR diseases may be because of its selective attenuation of Th17 cells, and also that novel therapeutics, which target either Th17 cells themselves or the effector memory T-helper cell population from which they are derived, would be strong candidates for drug development in the context of SR inflammation.
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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.