ArticleThe Journal of clinical endocrinology and metabolism2012
Dynamic development of glucocorticoid resistance during autoimmune neuroinflammation.
Article in The Journal of clinical endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- Gut-Brain Interactions and Their Impact on Astrocytes in the Context of Multiple Sclerosis and Beyond.Cells · 2024Review
- T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients.Cells · 2023Article
- Multiple sclerosis: Immunopathological heterogeneity and its implications.European journal of immunology · 2022Review
- Central stress processing, T-cell responsivity to stress hormones and disease severity in multiple sclerosis.Brain communications · 2022Article
- Methylprednisolone stimulated gene expression (GILZ, MCL-1) and basal cortisol levels in multiple sclerosis patients in relapse are associated with clinical response.Scientific reports · 2021Article
- MANF Is Neuroprotective in Early Stages of EAE, and Elevated in Spinal White Matter by Treatment With Dexamethasone.Frontiers in cellular neuroscience · 2021Article
- The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.Frontiers in neuroscience · 2021Article
- Glucocorticoid receptor mutations and clinical sensitivity to glucocorticoid in Chinese multiple sclerosis patients.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Article
- Altered Coupling of Psychological Relaxation and Regional Volume of Brain Reward Areas in Multiple Sclerosis.Frontiers in neurology · 2020Article
- Vitamin D increases glucocorticoid efficacy via inhibition of mTORC1 in experimental models of multiple sclerosis.Acta neuropathologica · 2019Article
- Disease- and treatment-associated acquired glucocorticoid resistance.Endocrine connections · 2018Review
- HIV and symptoms of depression are independently associated with impaired glucocorticoid signaling.Psychoneuroendocrinology · 2018Article
- Multiple Immune-Inflammatory and Oxidative and Nitrosative Stress Pathways Explain the Frequent Presence of Depression in Multiple Sclerosis.Molecular neurobiology · 2018Review
- Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Pregnancy and multiple sclerosis: from molecular mechanisms to clinical application.Seminars in immunopathology · 2016Review
- Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase.Clinical and experimental immunology · 2016Article
- Article
- Endogenous interleukin-6 amplifies interleukin-17 production and corticoid-resistance in peripheral T cells from patients with multiple sclerosis.Immunology · 2014Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
contextGlucocorticoids (GC) are powerful endogenous and therapeutic modulators of inflammation and play a critical role for controlling autoimmunity. GC resistance can be seen in patients with cell-mediated autoimmune disorders, but it is unknown whether this represents a stable trait or a state.
objectiveThe objective of the study was to determine whether GC resistance of T cell responses is dynamically regulated in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS).
designThis was a translational observational study. PATIENTS AND ANIMALS: EAE was induced in C57BL/6 mice. A cross-sectional sample of 25 patients with relapsing-remitting MS was included as well as four MS patients during pregnancy and postpartum.
main outcome measuresOutcome measures included GC sensitivity of T cell proliferation and GC-mediated apoptosis.
resultsGC resistance was seen in both autoantigen-specific and nonspecific responses of T cells obtained from mice with EAE. GC resistance preceded clinical symptoms and central nervous system infiltration of immune cells. T cells obtained during EAE were resistant to GC-induced apoptosis, and this was linked to down-regulation of GC receptor-α expression. GC resistance in T cells was also seen in MS patients with radiological evidence for ongoing inflammation. GC resistance was absent in the MS patients during pregnancy, when relapse risk is decreased, but recurred postpartum, a time of increased relapse risk.
conclusionsThese data demonstrate that GC resistance during autoimmune neuroinflammation is dynamically regulated. This has implications for the timing of steroid treatments and provides a putative pathway to explain the observed association between psychological stress and exacerbation of autoimmune diseases.
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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.