Dong Xiangyang, Bachman Lori A, Miller Melinda N, Nath Karl A, Griffin Matthew D
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Kidney Int. 2008 Nov;74(10):1294-309. doi: 10.1038/ki.2008.394. Epub 2008 Aug 13.
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.
急性尿路梗阻会导致间质炎症，伴有白细胞积聚和可溶性介质的分泌。在此我们表明，单侧输尿管结扎在梗阻后24 - 72小时会导致肾内F4/80(+)和F4/80(-)树突状细胞、单核细胞、中性粒细胞和T细胞逐渐增加。用氯膦酸盐预处理耗尽树突状细胞后发现，这些细胞是梗阻肾脏中肿瘤坏死因子和其他促炎介质的最主要来源。F4/80(+)树突状细胞和T细胞在梗阻肾脏的皮质-髓质交界处和皮质中共定位。发现梗阻肾脏中T细胞的细胞因子分泌模式和表面表型包括分泌干扰素-γ的CD4(+)和CD8(+)记忆T细胞以及分泌白细胞介素17（IL-17）的CD4(+)记忆T细胞。结扎前耗尽肾内树突状细胞在数量上并未减少梗阻肾脏中的T细胞，但减弱了具有干扰素-γ和IL-17活性的T细胞。我们的研究表明，肾内树突状细胞是急性尿路梗阻后以前未被认识的促炎介质早期来源，并且在包括分泌IL-17的CD4(+) T细胞在内的效应记忆T细胞的募集和激活中发挥特定作用。
