1. Academic Validation
  2. Renal macrophages monitor and remove particles from urine to prevent tubule obstruction

Renal macrophages monitor and remove particles from urine to prevent tubule obstruction

  • Immunity. 2023 Dec 22:S1074-7613(23)00534-4. doi: 10.1016/j.immuni.2023.12.003.
Jian He 1 Yangyang Cao 1 Qian Zhu 2 Xinge Wang 1 Guo Cheng 3 Qiang Wang 4 Rukun He 1 Haoran Lu 5 Yuancheng Weng 1 Genxiang Mao 6 Yizhong Bao 6 Jing Wang 7 Xiaoli Liu 8 Fei Han 9 Peng Shi 10 Xiao Z Shen 11
Affiliations

Affiliations

  • 1 Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 2 Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 3 Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 4 Department of Laboratory Medicine, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 5 Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining, Zhejiang, China.
  • 6 Zhejiang Provincial Key Lab of Geriatrics, Department of Geriatrics, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 7 Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 8 Department of Neurology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 9 Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 10 Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: ship@zju.edu.cn.
  • 11 Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: shenx@zju.edu.cn.
Abstract

When the filtrate of the glomerulus flows through the renal tubular system, various microscopic sediment particles, including mineral crystals, are generated. Dislodging these particles is critical to ensuring the free flow of filtrate, whereas failure to remove them will result in kidney stone formation and obstruction. However, the underlying mechanism for the clearance is unclear. Here, using high-resolution microscopy, we found that the juxtatubular macrophages in the renal medulla constitutively formed transepithelial protrusions and "sampled" urine contents. They efficiently sequestered and phagocytosed intraluminal sediment particles and occasionally transmigrated to the tubule lumen to escort the excretion of urine particles. Mice with decreased renal macrophage numbers were prone to developing various intratubular sediments, including kidney stones. Mechanistically, the transepithelial behaviors of medulla macrophages required Integrin β1-mediated ligation to the tubular epithelium. These findings indicate that medulla macrophages sample urine content and remove intratubular particles to keep the tubular system unobstructed.

Keywords

integrin beta1; kidney; kidney stone; macrophages; renal tubules.

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