gms | German Medical Science

42. Kongress der Deutschen Gesellschaft für Rheumatologie, 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 24. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

17.-20. September 2014, Düsseldorf

Article

Send article

SIGLEC-1 Expressing Plasmacytoid Dendritic Cells (pDCs) in Human Blood – A Role in SLE Pathogenesis?

Meeting Abstract

Search Medline for

  • Velia Gerl - Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Theresa Fischer - Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Adriano Taddeo - Deutsches Rheuma-Forschungszentrum (DRFZ), Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Oliver Winter - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Andrzej Dzionek - Miltenyi Biotec GmbH, Department of Research and Development, Bergisch Gladbach
  • Tobias Alexander - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Robert Biesen - Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
  • Andreas Radbruch - Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
  • Falk Hiepe - Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie der Charité - Universitätsmedizin Berlin und Deutsches RheumaForschungszentrum Berlin - ein Institut der Leibniz-Gemeinschaft, Berlin

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Düsseldorf, 17.-20.09.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocER.06

doi: 10.3205/14dgrh073, urn:nbn:de:0183-14dgrh0731

Published: September 12, 2014

© 2014 Gerl et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Background: Plasmacytoid dendritic cells (pDCs) are considered a crucial element in SLE pathogenesis due to their potency to produce high levels of IFN-α. This innate immunological function of pDCs is lost by terminal differentiation into a professional antigen-presenting cell, thereby upregulating costimulatory molecules and downregulating innate characteristics, e.g. IFN-α expression. Siglec-1 (sialoadhesin, CD169) is an adhesion molecule first characterized on cells of the macrophage-monocyte lineage. Expression of Siglec-1 on monocytes was identified as an IFN-α-regulated marker for active disease in SLE. Siglec-1 is suggested to play a role in the regulation of adaptive immune responses. The impact of Siglec-1 in adaptive immunity together with its nature as IFN-α regulated molecule prompted us to study Siglec-1 in pDCs with focus on SLE pathogenesis.

Methods: An 8-color-flowcytometric analysis was performed on whole blood of healthy donors and SLE patients. PDCs were identified by CD3-/CD19-/CD14-/CD123high//BDCA-2+/HLA-DR+ expression and characterized for Siglec-1, CD86 and CD83. IFN-α serum levels in SLE were measured in parallel. In vitro stimulation of intracellular IFN-α expression by TLR7 ligand Imiquimod-R837 was studied in MACS-sorted pDCs. Surface Siglec-1 induction by recombinant IFN-α was studied in monocytes, too.

Results: We found a small subpopulation of Siglec-1 expressing pDCs in human peripheral blood. Compared to Siglec-1 negative pDCs, Siglec-1 positive pDCs express significantly higher CD86 (Wilcoxon matched pairs test:p=0.0006, n=16) but not CD83. Functionally, Siglec-1 positive pDCs fail to express intracellular IFN-α via TLR-7. Siglec-1 positive pDCs in SLE correlate significantly with disease activity (rS=0.55, p=0.008, n=22) but not with IFN-α serum levels. Furthermore, Siglec-1 expression can be induced in vitro by IFN-α in monocytes but not in pDCs.

Conclusion: Siglec-1 positive pDCs might represent a distinct pDC subset exhibiting an adaptive rather than an innate immunological function which could play a role in the pathogenesis of SLE.