Systemic Lupus Erythematosus
Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: Role of interleukin-18
Article first published online: 28 DEC 2007
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 1, pages 251–262, January 2008
How to Cite
Tucci, M., Quatraro, C., Lombardi, L., Pellegrino, C., Dammacco, F. and Silvestris, F. (2008), Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: Role of interleukin-18. Arthritis & Rheumatism, 58: 251–262. doi: 10.1002/art.23186
- Issue published online: 28 DEC 2007
- Article first published online: 28 DEC 2007
- Manuscript Accepted: 7 SEP 2007
- Manuscript Received: 29 DEC 2006
- PRIN 2005
- University of Bari
Defective circulating dendritic cells (DCs) have been described in systemic lupus erythematosus (SLE) and correlated with high levels of interferon-α (IFNα). DCs are differentiated as being either myeloid or plasmacytoid, according to chemokine expression and the tendency to migrate toward inflamed tissue. We investigated the potential role of interleukin-18 (IL-18) in driving the glomerular migration of DCs in lupus nephritis (LN) and in affecting the ability of DCs to induce an imbalance in the Th1:Th2 ratio.
DC subsets were characterized by flow cytometry and defined as either myeloid or plasmacytoid according to the expression of CD11c/blood dendritic cell antigen 1 (BDCA-1) and CD123/BDCA-2, respectively. The serum Th1:Th2 profile was studied by enzyme-linked immunosorbent assay. IL-18 receptor (IL-18R) and other chemokine receptors were analyzed by flow cytometry. Glomerular levels of IL-18/IL-18R and the presence of plasmacytoid DCs and myeloid DCs were investigated by immunohistochemical analysis.
The number of peripheral plasmacytoid DCs was decreased in patients with SLE compared with control subjects, and this defect in the number of DCs was correlated with LN. Patients with LN showed a prevalent Th1 response, with high production of IL-18, IL-12 and IFNγ. Only plasmacytoid DCs expressed IL-18R. Patients with severe LN showed a high accumulation of IL-18 within glomeruli in association with the presence of plasmacytoid DCs, whereas myeloid DCs were almost absent.
A deficient number of peripheral plasmacytoid DCs correlated with high levels of Th1 cytokines and was associated with LN. Both serum and glomerular IL-18 were increased in LN. It is suggested that the high level of expression of IL-18R by peripheral plasmacytoid DCs allows the DCs to relocate within glomeruli under IL-18 stimulation and triggers the resident T cells, thus promoting renal damage.