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Blood dendritic cells in systemic lupus erythematosus exhibit altered activation state and chemokine receptor function
  1. Velia Gerl1,2,
  2. Alexandra Lischka1,2,
  3. Daniel Panne1,2,
  4. Patrick Großmann1,2,
  5. Rita Berthold1,2,
  6. Bimba Franziska Hoyer1,2,
  7. Robert Biesen1,
  8. Anne Bruns1,
  9. Tobias Alexander1,
  10. Annett Jacobi1,
  11. Thomas Dörner1,
  12. Gerd-Rüdiger Burmester1,
  13. Andreas Radbruch2,
  14. Falk Hiepe1,2
  1. 1Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
  2. 2German Rheumatism Research Centre – a Leibniz Institute, Berlin, Germany
  1. Correspondence to Professor Falk Hiepe, Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; falk.hiepe{at}charite.de

Abstract

Background Dendritic cells (DCs) have a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). Reduced numbers of blood DCs and the accumulation of DCs at inflammatory sites have been observed in SLE. One crucial feature of DCs is their ability to migrate.

Objective To analyse the maturation/activation state and the migratory capacity of different DC precursor subsets in SLE to further elucidate their role in autoimmunity.

Methods Plasmacytoid DCs (pDCs), myeloid DCs (mDCs) and monocytes from patients with SLE, healthy volunteers and healthy volunteers immunised with tetanus/diphtheria were examined by flow cytometry for expression of subset-specific antigens (BDCA-2, CD11c, CD14, HLA-DR), activation/maturation markers (CD83, CD86, CD40, BLyS) and chemokine receptors (CCR1, CCR5, CCR7, ChemR23). Additionally, migratory capacity to chemokine receptors was investigated in vitro using the chemokines RANTES, CCL19 and chemerin.

Results SLE monocytes and mDCs had higher CD86 and B-lymphocyte stimulatory factor (BLyS) expression levels. ChemR23 expression was lower in SLE pDCs and mDCs. Basal and CCL19-specific migration levels were higher in SLE pDCs. Altered DC function in SLE had no correlative changes in chemokine receptor expression, whereas immunisation-induced blood DC migration patterns in healthy donors were accompanied by changes in chemokine receptor expression.

Conclusions The phenotypic and migratory disturbances observed in SLE blood DCs could result in altered distribution of DCs in peripheral tissues, contributing to dysregulated immune responses and autoimmunity.

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Footnotes

  • VG and AL contributed equally.

  • Funding This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 421, C4).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Ethics Committee Charité.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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