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

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.

• Authors: Hui Han, Jinzhou Zhu, Yaqiong Wang, Zhengbin Zhu, Yanjia Chen, Lin Lu, Wei Jin, Xiaoxiang Yan, Ruiyan Zhang
• Journal: The Journal of pathology (J Pathol) Vol. 241 Issue 1 Pg. 80-90 (Jan 2017) ISSN: 1096-9896 [Electronic] England
• PMID: 27763657 (Publication Type: Journal Article)
• Copyright: © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Chemical References

• Ccl2 protein, mouse
• Chemokine CCL2
• Inflammation Mediators

Topics

• Animals
• B-Lymphocytes (immunology)
• Cell Movement (immunology)
• Chemokine CCL2 (antagonists & inhibitors, immunology)
• Chemotaxis, Leukocyte (immunology)
• Fibrosis
• Inflammation Mediators (metabolism)
• Kidney Diseases (etiology, immunology)
• Kidney Tubules (immunology, pathology)
• Male
• Mice, Inbred C57BL
• Monocytes (immunology)
• Ureteral Obstruction (complications, immunology)