1005 Characterization of regulatory receptors on plasmacytoid dendritic cells in lupus. (14th December 2022)

• Record Type: Journal Article
• Authors: Jensen, Mark A; Nln, Ilona; Iwamoto, Taro; Dorschner, Jessica M; Vsetecka, Danielle M; McCoy, Gabrielle A; Paredes, Jacqueline L; Niewold, Timothy B
• Is Part Of: Lupus science & medicine. Volume 9(2022)Supplement 3
• Page Start: A68
• Page End: A68
• Publication Date: 2022-12-14
• Subjects: Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1136/lupus-2022-lupus21century.65
• Languages: English
• ISSNs: 2398-8851

Abstract

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.