Separated parabiont reveals the fate and lifespan of peripheral-derived immune cells in normal and ischaemia-induced injured kidneys.

Separated parabiont reveals the fate and lifespan of peripheral-derived immune cells in normal and ischaemia-induced injured kidneys.
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分离的共生体揭示了正常和缺血引起的损伤肾脏中外周源性免疫细胞的命运和寿命

DOI:
10.1098/rsob.200340
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发表时间:
2021-06
期刊:
影响因子:
5.8
通讯作者:
Xu G
Xu G
中科院分区:
生物学2区
文献类型:
--
作者:
Deng X;Zhou C;Liao R;Guo Y;Wang Y;Li G;Wu J;Xu H;Hu Z;Pei G;Liao W;Yao Y;Yang Q;Zeng R;Xu G

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免疫细胞浸润在急性肾损伤(阿基)至慢性肾病(CKD)的进展中起关键作用。T淋巴细胞、嗜中性粒细胞、单核细胞/巨噬细胞和其他免疫细胞调节炎症、组织重塑和修复。为了确定各种免疫细胞群体积累的动力学,我们建立了一种结合联体共生和分离手术的动物模型,以探索迁移到肾脏的外周血白细胞的命运和寿命。我们发现,外周血T淋巴细胞可以存活很长时间(超过14天),而外周血中性粒细胞存活时间很短,在健康和缺血诱导的受损肾脏。在正常肾脏中,近一半的外周源性巨噬细胞在14天后消失,而它们在炎症肾脏中的存在时间延长。从循环单核细胞池中更新了一部分F4/80 high巨噬细胞。此外,我们发现肾缺血再灌注后,中性粒细胞在早期显著增加,T淋巴细胞主要在晚期积聚,而巨噬细胞在整个AKI-CKD进展过程中浸润,并且与正常肾脏相比,在损伤肾脏中持续时间更长。总之,外周来源的巨噬细胞、T淋巴细胞和中性粒细胞在肾脏中表现出不同的寿命,它们在AKI-CKD进展过程中可能发挥不同的作用。
Immune cell infiltration plays a key role in acute kidney injury (AKI) to chronic kidney disease (CKD) progression. T lymphocytes, neutrophils, monocytes/macrophages and other immune cells regulate inflammation, tissue remodelling and repair. To determine the kinetics of accumulation of various immune cell populations, we established an animal model combining parabiosis and separation surgery to explore the fate and lifespan of peripheral leucocytes that migrate to the kidney. We found that peripheral T lymphocytes could survive for a long time (more than 14 days), whereas peripheral neutrophils survived for a short time in both healthy and ischaemia-induced damaged kidneys. Nearly half of the peripheral-derived macrophages disappeared after 14 days in normal kidneys, while their existing time in the inflammatory kidneys was prolonged. A fraction of F4/80high macrophages were renewed from the circulating monocyte pool. In addition, we found that after renal ischaemia reperfusion, neutrophils increased significantly in the early phase, and T lymphocytes mainly accumulated in the late stage, whereas macrophages infiltrated throughout AKI-CKD progression and were sustained longer in injured as opposed to normal kidneys. In conclusion, peripheral-derived macrophages, T lymphocytes and neutrophils exhibit different lifespans in the kidney, which may play different roles during AKI-CKD progression.
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