Accumulation and therapeutic modulation of 6-sulfo LacNAc(+) dendritic cells in multiple sclerosis
| Autor: | Katja Thomas, Wolfgang Brück, Hayrettin Tumani, Rebekka Wehner, Thorsten Schultheiß, Imke Metz, Claudia Günther, Heinz Reichmann, Tjalf Ziemssen, Kristin Dietze, Marc Schmitz, Knut Schäkel |
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| Rok vydání: | 2014 |
| Předmět: |
business.industry
Multiple sclerosis medicine.disease Article 3. Good health Proinflammatory cytokine Pathogenesis Natalizumab Neurology Methylprednisolone Interferon Immunology Medicine multiple sclerosis dendritic cells Tumor necrosis factor alpha Neurology (clinical) Glatiramer acetate business medicine.drug |
| Zdroj: | Neurology® Neuroimmunology & Neuroinflammation |
| ISSN: | 2332-7812 |
| Popis: | OBJECTIVE: To examine the potential role of 6-sulfo LacNAc(+) (slan) dendritic cells (DCs) displaying pronounced proinflammatory properties in the pathogenesis of multiple sclerosis (MS). METHODS: We determined the presence of slanDCs in demyelinated brain lesions and CSF samples of patients with MS. In addition, we explored the impact of methylprednisolone, interferon-β, glatiramer acetate, or natalizumab on the frequency of blood-circulating slanDCs in patients with MS. We also evaluated whether interferon-β modulates important proinflammatory capabilities of slanDCs. RESULTS: SlanDCs accumulate in highly inflammatory brain lesions and are present in the majority of CSF samples of patients with MS. Short-term methylprednisolone administration reduces the percentage of slanDCs in blood of patients with MS and the proportion of tumor necrosis factor-α- or CD150-expressing slanDCs. Long-term interferon-β treatment decreases the percentage of blood-circulating slanDCs in contrast to glatiramer acetate or natalizumab. Furthermore, interferon-β inhibits the secretion of proinflammatory cytokines by slanDCs and their capacity to promote proliferation and differentiation of T cells. CONCLUSION: Accumulation of slanDCs in highly inflammatory brain lesions and their presence in CSF indicate that slanDCs may play an important role in the immunopathogenesis of MS. The reduction of blood-circulating slanDCs and the inhibition of their proinflammatory properties by methylprednisolone and interferon-β may contribute to the therapeutic efficiency of these drugs in patients with MS. peerReviewed |
| Databáze: | OpenAIRE |
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