Share

October 2014; 1 (3) ArticleOpen Access

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

Katja Thomas, Kristin Dietze, Rebekka Wehner, Imke Metz, Hayrettin Tumani, Thorsten Schultheiß, Claudia Günther, Knut Schäkel, Heinz Reichmann, Wolfgang Brück, Marc Schmitz, Tjalf Ziemssen
First published September 18, 2014, DOI: https://doi.org/10.1212/NXI.0000000000000033
Full PDF
Citation
Permissions

Make Comment

See Comments

Downloads
1381

Share

Abstract

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.

GLOSSARY

CTL=
cytotoxic T lymphocyte;
DC=
dendritic cell;
FCS=
fetal calf serum;
GA=
glatiramer acetate;
IFN=
interferon;
Ig=
immunoglobulin;
IL=
interleukin;
LPS=
lipopolysaccharide;
MP=
methylprednisolone;
MS=
multiple sclerosis;
NA=
natalizumab;
PBMC=
peripheral blood mononuclear cell;
PBS=
phosphate-buffered saline;
pDC=
plasmacytoid DC;
RRMS=
relapsing-remitting MS;
slan=
6-sulfo LacNAc+;
Th=
T helper;
TNF=
tumor necrosis factor

Footnotes

  • Go to Neurology.org/nn for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by Zentrale Rechungsstelle University Hospital, Dresden, Germany.

  • ↵* These authors contributed equally to the manuscript.

  • Received May 28, 2014.
  • Accepted in final form August 18, 2014.

This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

View Full Text

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. [email protected]
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
Advertisement

Related Articles

  • No related articles found.

Topics Discussed

Alert Me

Recommended articles