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Accumulation and therapeutic modulation of 6-sulfo LacNAc(+) dendritic cells in multiple sclerosis
Katja Thomas1, Kristin Dietze1, Rebekka Wehner1
1Departments of Neurology (K.T., T.S., H.R., T.Z.) and Dermatology (C.G.), University Hospital, Dresden; Institute of Immunology (K.D., R.W., M.S.), Medical Faculty, TU Dresden; Department of Neuropathology (I.M., W.B.), University Medical Centre, Göttingen; Department of Neurology (H.T.), University Hospital, Ulm; Department of Dermatology (K.S.), University Hospital, Heidelberg; and Center for Regenerative Therapies Dresden (M.S.), Dresden, Germany.
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.
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