Background

M1-type proinflammatory macrophages (MΦ) promote glomerular injury in lupus nephritis (LN). However, whether this phenotype is altered by steroid therapy is unclear. Therefore, we investigated the effect of steroid treatment on MΦ phenotype in LN.

Methods

Patients with LN (7–18 years old) were divided into 2 groups: those with no treatment (N) before biopsy (n = 17) and those who underwent steroid (S) treatment (3–73 days) before biopsy (n = 15). MΦ number and phenotype were assessed by immunofluorescence. In vitro studies used monocyte-derived MΦ from healthy volunteers.

Results

Age at biopsy, urine findings, and kidney function (eGFR) were comparable between the two groups. Biopsies in N group had higher levels of active lesions such as endocapillary hypercellularity, necrosis, and cellular crescent formation (p < 0.05). The total CD68+ MΦ infiltrate was comparable between N and S groups. However, N group had more M1 MΦ (CD68+ CD86+ cells) (p < 0.05) and fewer M2 MΦ (CD68+ CD163+ cells) (p < 0.05), giving a 6-fold increase in the M2/M1 ratio in S vs. N groups. Dexamethasone treatment of cultured MΦ induced upregulation of CD163 expression, increased production of anti-inflammatory (IL-10, IL-19) and profibrotic factors (FGF-22, PDGF), and upregulated the scavenger receptor, stabilin-1. Upregulation of stabilin-1 in CD163+ M2 MΦ was confirmed in biopsies from S group.

Conclusions

Initial steroid treatment induces MΦ phenotypic change from proinflammatory M1 to anti-inflammatory or profibrotic M2 in LN with acute/active lesions. Although steroid treatment is effective for resolution of M1-medated injury, promotion of fibrotic lesions via M2 MΦ is a potential downside of steroid single therapy in LN.

中文翻译：

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类固醇治疗促进儿童狼疮性肾炎的 M2 抗炎巨噬细胞表型。

背景

M1 型促炎巨噬细胞 (MΦ) 促进狼疮性肾炎 (LN) 的肾小球损伤。然而，这种表型是否会因类固醇治疗而改变尚不清楚。因此，我们研究了类固醇治疗对 LN 中 MΦ 表型的影响。

方法

LN 患者（7-18 岁）分为 2 组：活检前未治疗 (N) 组 ( n  = 17) 和活检前接受类固醇 (S) 治疗 (3-73 天) 者 ( n  = 15)。通过免疫荧光评估 MΦ 数量和表型。体外研究使用来自健康志愿者的单核细胞衍生的 MΦ。

结果

两组的活检年龄、尿液检查结果和肾功能 (eGFR) 具有可比性。 N 组活检有较高水平的活动性病变，如毛细血管内细胞过多、坏死和细胞新月体形成（p  < 0.05）。 N 组和 S 组之间的总 CD68+ MΦ 浸润是可比的。然而，N组有更多的M1 MΦ（CD68+ CD86+细胞）（p  < 0.05）和较少的M2 MΦ（CD68+ CD163+细胞）（p < 0.05)，使 S 组与 N 组的 M2/M1 比率增加 6 倍。地塞米松处理培养的 MΦ 诱导 CD163 表达上调，增加抗炎（IL-10、IL-19）和促纤维化因子（FGF-22、PDGF）的产生，并上调清道夫受体 stabilin-1。S 组活检证实 CD163+ M2 MΦ 中 stabilin-1 上调。

结论

在具有急性/活动性病变的 LN 中，初始类固醇治疗诱导 MΦ 表型从促炎 M1 变为抗炎或促纤维化 M2。尽管类固醇治疗对解决 M1 介导的损伤有效，但通过 M2 MΦ 促进纤维化病变是 LN 中类固醇单一治疗的潜在缺点。