The possible role of ChemR23/Chemerin axis in the recruitment of dendritic cells in lupus nephritis

Kidney Int. 2011 Jun;79(11):1228-35. doi: 10.1038/ki.2011.32. Epub 2011 Feb 23.

Abstract

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)-α and interferon-γ as measured by quantitative PCR and enzyme-linked immunosorbent assay. Interestingly, TNF-α 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Case-Control Studies
  • Cells, Cultured
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Chemotaxis*
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Endothelial Cells / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins
  • Interferon-gamma / metabolism
  • Kidney / immunology*
  • Kidney / pathology
  • Kidney Tubules, Proximal / immunology
  • Kidney Tubules, Proximal / pathology
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology
  • RNA, Messenger / metabolism
  • Receptors, Chemokine / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index
  • Signal Transduction*
  • Time Factors
  • Transendothelial and Transepithelial Migration*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CMKLR1 protein, human
  • Chemokines
  • Intercellular Signaling Peptides and Proteins
  • RARRES2 protein, human
  • RNA, Messenger
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma