Renal recruitment of B lymphocytes exacerbates tubulointerstitial fibrosis by promoting monocyte mobilization and infiltration after unilateral ureteral obstruction |
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| Authors: | Hui Han Jinzhou Zhu Yaqiong Wang Zhengbin Zhu Yanjia Chen Lin Lu Wei Jin Xiaoxiang Yan Ruiyan Zhang |
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| Affiliation: | 1. Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;2. Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;3. Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China |
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| Abstract: | 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. © 2016 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. |
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| Keywords: | B lymphocyte fibrosis CC chemokine ligand‐2 unilateral ureteral obstruction |
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