title: Dendritic cells facilitate accumulation of IL-17 T cells in the kidney following acute renal obstruction.
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.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Dong
authors.forename: Lori A
authors.initials: LA
authors.lastname: Bachman
authors.forename: Melinda N
authors.initials: MN
authors.lastname: Miller
authors.forename: Karl A
authors.initials: KA
authors.lastname: Nath
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Griffin
mesh_terms: 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*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17