虽然“多因素引发”理论被广泛认可为IgA肾病(IgAN)的发病机制，但越来越多的证据表明单核/巨噬细胞系统在IgAN的进展中起重要作用，然而具体机制尚不清楚。在本研究中，我们调查了15项研究中的1067名患者，发现每个肾小球内的巨噬细胞数量与血尿程度呈正相关，肾活检中肾小球内的巨噬细胞主要与系膜增殖(M)相关。在肾小管间质中，巨噬细胞与间质α-SMA和NF-kB的表达、间质病变、小管萎缩/间质纤维化(T)和节段性肾小球硬化(S)显著相关。在肾小球和肾小管间质中，根据牛津MEST-C分类，M1占85.41%；在血液中，M1占100%。CD89+单核细胞均匀荧光强度低的患者显示更严重的病理特征(S1和T1-2)和临床症状。M1(CD80+)巨噬细胞与急性期的前炎症有关，而M2(CD163+)巨噬细胞参与组织修复和重塑，与慢性炎症相关。在肾小球中，M2巨噬细胞通过分泌细胞因子如IL-10和肿瘤坏死因子β(TGF-β)激活肾小球基质扩张，而M0(CD68+)巨噬细胞刺激肾小球过度细胞增多。在肾小管间质中，M2巨噬细胞在肾纤维化和硬化中起关键作用。巨噬细胞被认为是抗原呈递细胞，能激活T细胞并释放多种细胞因子刺激炎症反应。浸润肾小球的巨噬细胞通过系膜-足细胞-小管的相互作用及对小管的损伤破坏了足细胞的完整性。 版权所有©2023 Liu, Gong和Xu。

Although the "multiple hits" theory is a widely accepted pathogenesis in IgA nephropathy (IgAN), increasing evidence suggests that the mononuclear/macrophage system plays important roles in the progression of IgAN; however, the exact mechanism is unclear. In the present study, we explored 1,067 patients in 15 studies and found that the number of macrophages per glomerulus was positively related with the degree of hematuria, and the macrophages in the glomeruli were mainly related to mesangial proliferation (M) in renal biopsy. In the tubulointerstitium, macrophages were significantly paralleled to tubulointerstitial α-SMA and NF-kB expression, tubulointerstitial lesion, tubule atrophy/interstitial fibrosis (T), and segmental glomerulosclerosis (S). In the glomeruli and tubulointerstitium, M1 accounted for 85.41% in the M classification according to the Oxford MEST-C, while in the blood, M1 accounted for 100%, and the patients with low CD89+ monocyte mean fluorescence intensity displayed more severe pathological characteristics (S1 and T1-2) and clinical symptoms. M1 (CD80+) macrophages were associated with proinflammation in the acute phase; however, M2 (CD163+) macrophages participated in tissue repair and remodeling, which correlated with chronic inflammation. In the glomeruli, M2 macrophages activated glomerular matrix expansion by secreting cytokines such as IL-10 and tumor necrosis factor-β (TGF-β), and M0 (CD68+) macrophages stimulated glomerular hypercellularity. In the tubulointerstitium, M2 macrophages played pivotal roles in renal fibrosis and sclerosis. It is assumed that macrophages acted as antigen-presenting cells to activate T cells and released diverse cytokines to stimulate an inflammatory response. Macrophages infiltrating glomeruli destroy the integrity of podocytes through the mesangio-podocytic-tubular crosstalk as well as the injury of the tubule.Copyright © 2023 Liu, Gong and Xu.