Dendritic cells facilitate accumulation of IL-17 T cells in the kidney following acute renal obstruction.
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.
Dong
Xiangyang
X
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Bachman
Lori A
LA
Miller
Melinda N
MN
Nath
Karl A
KA
Griffin
Matthew D
MD
D000208:Acute Disease; D000818:Animals; D016207:Cytokines; D003713:Dendritic Cells / Q000276:immunology*; D018836:Inflammation Mediators; D020381:Interleukin-17; D007668:Kidney / Q000276:immunology; D007674:Kidney Diseases / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014517:Ureteral Obstruction / Q000276:immunology*
D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17