Renal recruitment of B lymphocytes exacerbates tubulointerstitial fibrosis by promoting monocyte mobilization and infiltration after unilateral ureteral obstruction

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• 作者：Hui Han ; Jinzhou Zhu ; Yaqiong Wang ; Zhengbin Zhu ; Yanjia Chen ; Lin Lu ; Wei Jin ; Xiaoxiang Yan and Ruiyan Zhang
• 刊名：The Journal of Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：241
• 期：1
• 页码：80-90
• 全文大小：6913K
• ISSN：1096-9896

文摘

Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells, and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B-cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B-cell-deficient μMT mice or CD20 antibody-mediated B-cell-depleted mice. Obstructed kidneys of μMT and anti-CD20-treated mice showed lower levels of monocyte/macrophage infiltration and collagen deposition compared to wild-type mice. Mechanistically, anti-CD20 attenuated UUO-induced alterations of renal tumour necrosis factor-α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) pro-inflammatory genes, and CC chemokine ligand-2 (CCL2) essential for monocyte recruitment; B cells were one of the main sources of CCL2 in post-UUO kidneys. Neutralization of CCL2 reduced monocyte/macrophage influx and fibrotic changes in obstructed kidneys. Therefore, early-stage accumulation of B cells in the kidney accelerated monocyte/macrophage mobilization and infiltration, aggravating the fibrosis resulting from acutely induced kidney nephropathy.