Dendritic cells facilitate accumulation of IL-17 T cells in the kidney following acute renal obstruction

Kidney Int. 2008 Nov;74(10):1294-309. doi: 10.1038/ki.2008.394. Epub 2008 Aug 13.

Abstract

Acute urinary obstruction causes interstitial inflammation with leukocyte accumulation and the secretion of soluble mediators. Here we show that unilateral ureteral ligation caused a progressive increase in renal F4/80(+) and F4/80(-) dendritic cells, monocytes, neutrophils and T-cells 24-72 h following obstruction. Depletion of dendritic cells by clodronate pretreatment showed these cells to be the most potent source of tumor necrosis factor and other pro-inflammatory mediators in the obstructed kidney. F4/80(+) dendritic cells and T-cells co-localized in the cortico-medullary junction and cortex of the obstructed kidney. Cytokine secretion patterns and surface phenotypes of T-cells from obstructed kidneys were found to include interferon-gamma-secreting CD4(+) and CD8(+) memory T-cells as well as interleukin 17 (IL-17)-secreting CD4(+) memory T-cells. Depletion of the intra-renal dendritic cells prior to ligation did not numerically reduce T-cells in obstructed kidneys but attenuated interferon-gamma and IL-17-competent T-cells. Our study shows that intra-renal dendritic cells are a previously unidentified early source of proinflammatory mediators after acute urinary obstruction and play a specific role in recruitment and activation of effector-memory T-cells including IL-17-secreting CD4(+) T-cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Animals
  • Cytokines
  • Dendritic Cells / immunology*
  • Inflammation Mediators
  • Interleukin-17*
  • Kidney / immunology
  • Kidney Diseases / immunology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology*
  • Ureteral Obstruction / immunology*

Substances

  • Cytokines
  • Inflammation Mediators
  • Interleukin-17