Department of Nephrology, The First Hospital of Jilin University, Changchun 130021, Jilin, China.
Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, Jilin, China.
Int Immunopharmacol. 2021 Aug;97:107666. doi: 10.1016/j.intimp.2021.107666. Epub 2021 May 28.
T-cell immunoglobulin and mucin-domain-containing protein-3 (Tim-3) plays multiple important roles in immune response and participates in the pathogenesis of various inflammatory diseases by regulating macrophage polarization. However, its functions in the development of IgA nephropathy (IgAN) are still unclear. In this study, changes in the relative levels of Tim-3 monocytes/macrophages in peripheral blood and renal tissue, and their clinical significance in patients with IgAN were investigated. The expression of CD68 and Tim-3 in macrophages from patients with IgAN was determined via immunohistochemistry and immunofluorescence staining assays. Peripheral blood of 48 patients with biopsy-proven IgAN and 18 healthy controls (HCs) was collected to determine the frequency of circulating CD14Tim-3 cells using flow cytometry, before and after 24 weeks of prednisolone treatment. Serum interleukin (IL)-10 and tumor necrosis factor α (TNF-α) levels were measured using enzyme-linked immunosorbent assays. The potential association between clinical signs and Tim-3 monocytes/macrophages was analyzed. The percentages of circulating CD14Tim-3 monocytes were higher in samples from patients with IgAN than in those from HCs and were positively associated with the pathological features (segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis) of IgAN, according to the Oxford classification. Tissue staining assays revealed cells positive for both CD68 and Tim-3 in tubulointerstitial lesions of IgAN patients. In addition, elevated levels of serum IL-10 and TNF-α were detected in these patients in comparison to HCs. Furthermore, the frequency of circulating CD14Tim-3 monocytes had a positive correlation with levels of 24-h urinary protein and serum IL-10, and was negatively associated with renal function. After 24 weeks of treatment with prednisolone, the percentages of CD14Tim-3 cells were significantly reduced. In summary, our findings indicate that Tim-3 monocytes/macrophages might be involved in the pathogenesisof IgAN and could be used as a potential indicator to evaluate disease severity.
T 细胞免疫球蛋白和粘蛋白结构域蛋白 3（Tim-3）在免疫反应中发挥多种重要作用，并通过调节巨噬细胞极化参与各种炎症性疾病的发病机制。然而，其在 IgA 肾病（IgAN）中的作用尚不清楚。本研究旨在探讨外周血和肾组织中 Tim-3 单核细胞/巨噬细胞的相对水平变化及其在 IgAN 患者中的临床意义。通过免疫组化和免疫荧光染色检测 IgAN 患者巨噬细胞中 CD68 和 Tim-3 的表达。采用流式细胞术检测 48 例经肾活检证实的 IgAN 患者和 18 例健康对照者（HCs）外周血中循环 CD14Tim-3 细胞的频率，在给予泼尼松龙治疗 24 周前后分别进行检测。采用酶联免疫吸附试验检测血清白细胞介素（IL）-10 和肿瘤坏死因子-α（TNF-α）水平。分析临床指标与 Tim-3 单核细胞/巨噬细胞的潜在相关性。结果显示，与 HCs 相比，IgAN 患者的外周血中循环 CD14Tim-3 单核细胞比例更高，且与 IgAN 的病理特征（节段性肾小球硬化和肾小管萎缩/间质纤维化）呈正相关，根据牛津分类。组织染色检测结果显示，IgAN 患者的肾小管间质病变中存在同时表达 CD68 和 Tim-3 的细胞。此外，与 HCs 相比，这些患者的血清中 IL-10 和 TNF-α 水平升高。此外，循环 CD14Tim-3 单核细胞的频率与 24 小时尿蛋白和血清 IL-10 水平呈正相关，与肾功能呈负相关。经泼尼松龙治疗 24 周后，CD14Tim-3 细胞的比例显著降低。综上所述，本研究结果表明，Tim-3 单核细胞/巨噬细胞可能参与了 IgAN 的发病机制，可作为评估疾病严重程度的潜在指标。
