| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Makrygiannakis, Dimitrios Revu, Shankar Neregård, Petra af Klint, Erik Snir, Omri Grundtman, Cecilia Catrina, Anca Irinel |
| Abstract | Introduction Rheumatoid arthritis (RA) is characterized by synovial inflammation with local accumulation of mononuclear cells such as macrophages and lymphocytes. We previously demonstrated that intra-articular glucocorticoids decrease the synovial tissue (ST) T-cell population and therefore aimed to investigate whether this is mediated through modulation of apoptosis. Methods Apoptosis and cell phenotype were evaluated by immunohistochemistry and dual-immunofluorescence in synovial biopsy sections from 12 RA patients before and after a mean of 11 days of an intra-articular triamcinolone knee injection. In vitro, RA synovial fluid (SF)-derived T cells were evaluated for Annexin V expression by multicolor flow cytometry after 24-hour exposure to dexamethasone, methylprednisolone, or triamcinolone. We also tested induction of apoptosis by dexamethasone on psoriatic arthritis SF-derived T cells using the same method. Results Intra-articular glucocorticoids reduced ST T cells but not macrophage number. ST apoptosis levels were unchanged following treatment, virtually absent from lymphoid aggregates, and minimal in CD3+ cells both before and after treatment. RA SF T cells were resistant to glucocorticoid-induced apoptosis when cultured in the presence of monocytes but were rendered sensitive to all three tested compounds upon SF isolation. Furthermore, transwell coculture of monocytes and T cells demonstrated that soluble factor(s) and not cellular contact are essential for T-cell resistance to glucocorticoid-mediated apoptosis. This feature is RA-specific as far as dexamethasone-induced apoptosis in nonisolated SF T cells obtained from psoriatic arthritis patients is concerned. Conclusions We demonstrate that monocytes rescue synovial T cells from glucocorticoid-induced apoptosis, a feature that is specific for RA. To overcome this, we propose the use of monocyte-targeted therapies rather than T-cell apoptosis-inducing therapies. |
| Related Links | https://arthritis-research.biomedcentral.com/counter/pdf/10.1186/ar2582.pdf |
| Ending Page | 9 |
| Page Count | 9 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14786362 |
| DOI | 10.1186/ar2582 |
| Journal | Arthritis Research & Therapy |
| Issue Number | 6 |
| Volume Number | 10 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2008-12-19 |
| Access Restriction | Open |
| Subject Keyword | Rheumatology Orthopedics Rheumatoid Arthritis Glucocorticoid Synovial Fluid Synovial Tissue Triamcinolone |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology Rheumatology |
| Journal Impact Factor | 4.4/2023 |
| 5-Year Journal Impact Factor | 4.9/2023 |
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