Journal
KIDNEY INTERNATIONAL
Volume 79, Issue 11, Pages 1228-1235Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ki.2011.32
Keywords
chemokine; chemokine receptor; lupus nephritis; systemic lupus erythematosus
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Funding
- MIUR (Ministero dell'Istruzione Universita e Ricerca)
- Istituto Superiore di Sanita (ISS)
- University of Bari
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Dendritic cells (DCs) have a pivotal role in the autoimmune response of systemic lupus erythematosus. Plasmacytoid DCs infiltrate the kidney of patients with lupus nephritis, but factors regulating their recruitment to the kidney are unknown. Chemerin is the recently identified natural ligand of ChemR23, a receptor highly expressed by plasmacytoid DCs. We performed immunohistochemical and immunofluorescence analysis to study the ChemR23/chemerin axis in renal biopsies from patients with lupus nephritis. We found ChemR23-positive DCs had infiltrated the kidney tubulointerstitium in patients with severe lupus nephritis. Chemerin association with tubular epithelial cells and renal lymphatic endothelial cells was found in patients with lupus nephritis but not in normal kidneys. Proximal tubular epithelial cells produced chemerin in vitro, which was significantly down-modulated by added tumor necrosis factor (TNF)-alpha and interferon-gamma as measured by quantitative PCR and enzyme-linked immunosorbent assay. Interestingly, TNF-alpha was capable of inducing a functionally active form of renal chemerin, resulting in an efficient transendothelial migration of plasmacytoid DCs measured in transwell systems. Thus, the ChemR23/chemerin axis may have a role in the recruitment of DCs within the kidney in patients affected by lupus nephritis. Kidney International (2011) 79, 1228-1235; doi:10.1038/ki.2011.32; published online 23 February 2011
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