Article Text

Download PDFPDF

1005 Characterization of regulatory receptors on plasmacytoid dendritic cells in lupus
  1. Mark A Jensen1,
  2. Ilona Nln1,
  3. Taro Iwamoto2,
  4. Jessica M Dorschner3,
  5. Danielle M Vsetecka3,
  6. Gabrielle A McCoy3,
  7. Jacqueline L Paredes1 and
  8. Timothy B Niewold1
  1. 1Department of Medicine, Division of Rheumatology, Hospital for Special Surgery, New York, NY
  2. 2Allergy and Clinical Immunology, Chiba University, Japan
  3. 3Department of Immunology and Division of Rheumatology, Mayo Clinic, Rochester, MN

Abstract

Regulatory or suppressive receptors on plasmacytoid dendritic cells (PDCs) are an attractive therapeutic target in systemic lupus erythematosus (SLE), given the role type I interferon (IFN) plays in this disease. In this study, we determine whether SLE patient PDC regulatory receptor expression and function associates with disease features in SLE. We used quantitative multicolor flow cytometry to measure regulatory receptors on PDCs from SLE patients and control subjects, including immunoglobulin like transcript 7 (ILT7), bone marrow derived antigen 2 (BDCA2), ILT3, leukocyte-associated immunoglobulin-receptor 1 (LAIR1), natural killer cell P44-related protein (NKp44), bone marrow stromal cell antigen 2 (BST2), and dendritic cell (DC) immunoreceptor (DCIR). For functional studies, cells from 9 SLE patients and 9 controls were treated with ILT7 and BDCA2 crosslinking antibodies followed by TLR9 agonists. ILT7 and BDCA2 expression on SLE patient PDCs were inversely correlated with disease activity by SLEDAI score. High IFN SLE patients had increased levels of the ILT7 ligand BST2, and at the same time reduced ILT7 expression. BDCA2 levels were 5-fold higher than ILT7 levels, and crosslinking ILT7 only weakly inhibited IFN secretion. Crosslinking BDCA2 significantly reduced IFN production in SLE patient cells, but this effect on IFN was much greater in patients with low SLEDAI scores than those with high SLEDAI scores. In conclusion, we identify associations between PDC regulatory receptor expression and clinical disease in SLE, and dominant inhibitory function of BDCA2 over ILT7 in PDC type I IFN secretion with dependency upon disease activity.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.