Accumulation and therapeutic modulation of 6-sulfo LacNAc(+) dendritic cells in multiple sclerosis

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-beta, glatiramer acetate, or natalizumab on the frequency of blood-circulating slanDCs in patients with MS. We also evaluated whether interferon-beta 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-a-or CD150-expressing slanDCs. Long-term interferon-beta treatment decreases the percentage of blood-circulating slanDCs in contrast to glatiramer acetate or natalizumab. Furthermore, interferon-b 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-b may contribute to the therapeutic efficiency of these drugs in patients with MS.