CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis.
CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis.
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CD163+ M2C样巨噬细胞在狼疮肾炎患者的肾脏活检中占主导地位。
DOI：
10.1186/s13075-016-0989-y
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发表时间：
2016-04-18
影响因子：
4.9
通讯作者：
Daniel C
中科院分区：
文献类型：
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作者：
Olmes G;Büttner-Herold M;Ferrazzi F;Distel L;Amann K;Daniel C
巨噬细胞在狼疮肾炎发病机制中的作用，特别是它们分化为某种亚型（例如，M1或M2样）调节炎症反应，是未知的。在这里，我们研究了M1或M2样巨噬细胞的分化是否取决于狼疮肾炎的分期，以及这是否与临床参数相关。使用免疫组织化学分析，我们分析了68例狼疮性肾炎（ISN/RPS II-V级）患者的肾活检组织中M1样（iNOS+/CD 68+）、M2 a样（CD 206 +/CD 68+）、M2 c样巨噬细胞（CD 163 +/CD 68+）和FoxP 3+调节性T细胞的浸润。此外，肾活检时的临床参数，即，使用斯皮尔曼检验将血压、蛋白尿和血清尿素与巨噬细胞浸润相关。CD 68+巨噬细胞的平均数量与诊断的ISN/RPS类别相关，在弥漫性IV类活检中显示最高的巨噬细胞浸润，而在ISN/RPS V类中显示最低的数量。在所有ISN/RPS类别中，我们检测到M2 c样CD 163 +/CD 68+细胞多于M2 a样CD 206 +/CD 68+细胞，而M1-巨噬细胞仅起次要作用。聚类分析使用巨噬细胞亚型数量在不同的肾室揭示了三个主要的集群显示集群1为主的V类。集群2和3为主的狼疮IV类，表明这一类可以进一步区分其巨噬细胞群体。肾小管间质FoxP 3+细胞的数量与所有研究的巨噬细胞亚型相关，显示与M2 a样巨噬细胞数量的最强关联。通过血清肌酐和血清尿素评估的肾功能与肾小管上皮细胞中总CD 68+、M2 a样和M2 c样巨噬细胞的数量呈正相关。此外，总CD 68+和M2 c样巨噬细胞数量与Austin活动评分高度相关。有趣的是，在高血压狼疮患者中，与血压正常的狼疮患者的活检相比，只有M2 a样巨噬细胞的数量显著增加。M2样巨噬细胞是人类狼疮肾炎中的主要亚群，特别是M2 a亚群与疾病进展相关，但它们在疾病进展中的作用仍不清楚。
The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters. Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II–V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test. The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients. M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.