Analysis of TNF-mediated recruitment and activation of glomerular dendritic cells in mouse kidneys by compartment-specific flow cytometry

Kidney Int. 2013 Jul;84(1):116-29. doi: 10.1038/ki.2013.46. Epub 2013 Mar 6.


Renal dendritic cells (DCs) form an interstitial network contributing to inflammatory and adaptive immune responses in the kidney. The presence and functional role of DC-like glomerular CD11c(+) mononuclear phagocytes is a matter of debate. Using compartment-specific flow cytometry we found that healthy mouse kidneys contained 1.3 CD11c(+) cells per 100 glomeruli and these increased by 4.6-fold and 13-fold after TNF stimulation and immune complex deposition, respectively. Compartment-specific mRNA expression revealed a predominantly glomerular expression of TNF receptors, chemokines, and adhesion molecules; all upregulated after TNF exposure. Intraperitoneal TNF injection induced influx of neutrophils and mononuclear phagocytes including DC-like CD11c(+) cells into both the glomerular and tubulointerstitial compartments, but reduced in TNF receptor (Tnfr) 1-deficient mice. Additionally, Tnfr2 deficiency impaired glomerular infiltration of CD11c(+) cells, but not neutrophils. Interstitial CD11c(+) cells infiltrated in the presence of Tnfr1 or Tnfr2. TNF exposure also induced similar maturation of glomerular and interstitial CD11c(+) cells as demonstrated by increased surface expression of MHC II, CD54, and costimulatory molecules CD40, CD80, and CD86. Thus, by compartment-specific flow cytometry we could demonstrate the constitutive presence of DC-like CD11c(+) mononuclear phagocytes in normal mouse glomeruli and their TNF-induced accumulation and activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • CD11c Antigen / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Separation / methods*
  • Chemokines / genetics
  • Chemokines / metabolism
  • Chemotaxis*
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Female
  • Flow Cytometry*
  • Inflammation Mediators / metabolism*
  • Kidney Glomerulus / immunology*
  • Kidney Glomerulus / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephritis, Interstitial / genetics
  • Nephritis, Interstitial / immunology*
  • Nephritis, Interstitial / pathology
  • Phagocytes / immunology*
  • Phenotype
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor, Type I / deficiency
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type II / deficiency
  • Receptors, Tumor Necrosis Factor, Type II / genetics
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism*
  • Ureteral Obstruction / complications


  • Biomarkers
  • CD11c Antigen
  • Cell Adhesion Molecules
  • Chemokines
  • Inflammation Mediators
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tnfrsf1a protein, mouse
  • Tumor Necrosis Factor-alpha