Prednisolone treatment induces tolerogenic dendritic cells and a regulatory milieu in myasthenia gravis patients
Open accessAbstract
FOXP3-expressing naturally occurring CD4(+)CD25(high) T regulatory cells (Treg) are relevant in the control of autoimmunity, and a defect in this cell population has been observed in several human autoimmune diseases. We hypothesized that altered functions of peripheral Treg cells might play a role in the immunopathogenesis of myasthenia gravis, a T cell-dependent autoimmune disease characterized by the presence of pathogenic autoantibodies specific for the nicotinic acetylcholine receptor. We report in this study a significant decrease in the in vitro suppressive function of peripheral Treg cells isolated from myasthenia patients in comparison to those from healthy donors. Interestingly, Treg cells from prednisolone-treated myasthenia gravis patients showed an improved suppressive function compared with untreated patients, suggesting that prednisolone may play a role in the control of the peripheral regulatory network. Indeed, prednisolone treatment prevents LPS-induced maturation of monocyte-derived dendritic cells by hampering the up-regulation of costimulatory molecules and by limiting secretion of IL-12 and IL-23, and enhancing IL-10. In addition, CD4(+) T cells cultured in the presence of such tolerogenic dendritic cells are hyporesponsive and can suppress autologous CD4(+) T cell proliferation. The results shown in this study indicate that prednisolone treatment promotes an environment that favors immune regulation rather than inflammation.
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Glucocorticoids can convert dendritic cells to tolerogenic cells that promote regulatory T cell production, and this effect relies on glucocorticoid-mediated expression of GILZ.
“GCs can also convert DCs to tolerogenic cells, which promote the production of regulatory T cells (38, 39). This immunosuppressive effect critically relies on the GC-mediated expression of glucocorticoid-induce leucine zipper (GILZ), since this transcription factor appears as both necessary and sufficient for the induction of a tolerogenic state (40, 41).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [38]
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- Authors
- Luther, C., Adamopoulou, E., Stoeckle, C., Brucklacher-Waldert, V., Rosenkranz, D., Stoltze, L., Lauer, S., Poeschel, S., Melms, A., & Tolosa, E.
- Affiliations
- Hertie Institute for Clinical Brain Research (DE)
- University of Würzburg (DE)
- BC Cancer Agency (CA)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07
- Volume
- 183
- Issue
- 2
- Pages
- 841-848
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1844780367
- Cited by
- 93
- References
- 61
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 11 · 2014: 6 · 2013: 2 · 2012: 10
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- myasthenia gravis, prednisolone, regulatory T cells, Foxp3, tolerogenic dendritic cells, monocyte-derived dendritic cells, dendritic cell maturation, costimulatory molecules, IL-10, IL-12, IL-23, CD4+ T cell suppression, immunosuppressive therapy, autoimmunity
- MeSH terms
- Adult, Aged, Aged, 80 and over, Dendritic Cells, Humans, Immune Tolerance, Interleukins, Lipopolysaccharides, Middle Aged, Myasthenia Gravis, Prednisolone, Autoimmunity, Case-Control Studies, Coculture Techniques, Cell Proliferation, T-Lymphocytes, Regulatory
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