Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Exp Biol Med (Maywood). 2023 Feb;248(3):242-252. doi: 10.1177/15353702221147561. Epub 2023 Jan 20.
Intestinal mucosa barrier injury and immunity imbalance contribute to chronic kidney disease (CKD) progression. Type 3 innate lymphoid cells (ILC3s) are essential for normal intestinal homeostasis. Nevertheless, the relationship between ILC3s and CKD remains largely unknown. The aim of this study was to investigate the relationship linking ILC3s to clinical indicators among patients with renal dysfunction. The levels of circulating ILC3s and dendritic cells, as well as their subsets, in patients with renal dysfunction and healthy controls were determined through flow cytometry. The levels of human plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using enzyme-linked immunosorbent assay. Renal function was evaluated by measuring the estimated glomerular filtration rate (eGFR), as well as the levels of serum creatinine, blood urea nitrogen (BUN), and uric acid. The results revealed that the proportion of peripheral ILC3s was significantly decreased in patients with renal dysfunction. This reduction was positively associated with the levels of eGFR, and inversely associated with the levels of BUN and uric acid. Similarly, the percentage of circulating C-C motif chemokine receptor 6-positive (CCR6 ) ILC3s was also obviously reduced, and demonstrated positive and negative associations with the levels of eGFR and BUN, respectively. Furthermore, the levels of CCR6 ILC3s correlated positively with those of GM-CSF, as well as type 1 conventional dendritic cells (cDC1s), which also decreased in parallel with kidney function. Thus, the reduction of ILC3s, particularly CCR6 ILC3s, was related to worsening kidney function in patients with renal dysfunction. This effect may delay renal function impairment by regulating cDC1s via the secretion of GM-CSF, indicating that CCR6 ILC3s may serve as efficient biomarkers for evaluating kidney function.
肠黏膜屏障损伤和免疫失衡导致慢性肾脏病（CKD）进展。3 型固有淋巴细胞（ILC3）对于正常的肠道稳态至关重要。然而，ILC3 与 CKD 之间的关系在很大程度上仍然未知。本研究旨在探讨与肾功能障碍患者临床指标相关的 ILC3 关系。通过流式细胞术测定肾功能障碍患者和健康对照者循环 ILC3 和树突状细胞及其亚群的水平，采用酶联免疫吸附试验测定人血浆粒细胞-巨噬细胞集落刺激因子（GM-CSF）的水平。通过测量估计肾小球滤过率（eGFR）以及血清肌酐、血尿素氮（BUN）和尿酸水平来评估肾功能。结果显示，肾功能障碍患者外周血 ILC3 比例明显降低。这种减少与 eGFR 水平呈正相关，与 BUN 和尿酸水平呈负相关。同样，循环 C-C 基序趋化因子受体 6 阳性（CCR6+）ILC3 的百分比也明显降低，与 eGFR 和 BUN 水平呈正相关和负相关。此外，CCR6+ILC3 水平与 GM-CSF 以及 1 型传统树突状细胞（cDC1）呈正相关，cDC1 也与肾功能平行下降。因此，ILC3 的减少，特别是 CCR6+ILC3 的减少与肾功能障碍患者肾功能恶化有关。这种作用可能通过分泌 GM-CSF 调节 cDC1 来延迟肾功能损害，表明 CCR6+ILC3 可能作为评估肾功能的有效生物标志物。
