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Renal recruitment of B lymphocytes exacerbates tubulointerstitial fibrosis by promoting monocyte mobilization and infiltration after unilateral ureteral obstruction
Author(s) -
Han Hui,
Zhu Jinzhou,
Wang Yaqiong,
Zhu Zhengbin,
Chen Yanjia,
Lu Lin,
Jin Wei,
Yan Xiaoxiang,
Zhang Ruiyan
Publication year - 2017
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4831
Subject(s) - monocyte , medicine , fibrosis , chemokine , ccl2 , kidney , pathology , infiltration (hvac) , macrophage , immunology , immune system , biology , biochemistry , physics , in vitro , thermodynamics
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.