A subset of CD163+ macrophages displays mixed polarizations in discoid lupus skin.
A subset of CD163+ macrophages displays mixed polarizations in discoid lupus skin.
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DOI：
10.1186/s13075-015-0839-3
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发表时间：
2015-11-13
影响因子：
4.9
通讯作者：
Mohan C
中科院分区：
文献类型：
--
作者：
Chong BF;Tseng LC;Hosler GA;Teske NM;Zhang S;Karp DR;Olsen NJ;Mohan C
盘状红斑狼疮（DLE）患者的皮损皮肤含有巨噬细胞，其极化作用尚待研究。为了验证我们的假设，即 M1 巨噬细胞在 DLE 皮肤中会增加，我们通过使用基因表达和组织化学方法检查了 DLE 和正常皮肤中免疫细胞基因表达和巨噬细胞特征的转录组变化。通过微阵列和定量实时聚合酶链式反应 (RT-PCR) 比较 DLE 病变和正常对照皮肤的 RNA 基因表达。通过免疫组织化学分析两个皮肤组的 CD163 表达。进行双重免疫荧光研究来表征 CD163+ 巨噬细胞的蛋白质表达。与正常皮肤相比，DLE 皮肤的上调基因数量是下调基因数量的两倍。基因集富集分析将 DLE 和正常皮肤中的差异表达基因与之前发表的与 M1 和 M2 巨噬细胞相关的基因集进行比较，结果显示 DLE 皮肤和 M1 巨噬细胞中上调的基因之间存在很强的重叠。定量 RT-PCR 显示，多个 M1 巨噬细胞相关基因，例如趋化因子（C-X-C 基序）配体 10 (CXCL10)、趋化因子（C-C 基序）配体 5 (CCL5) 和信号转导子和转录激活子 1 (STAT1)，在 DLE 皮肤中的 mRNA 水平有所增加。与正常皮肤相比，DLE 皮肤表皮-真皮交界处附近和血管周围区域的 CD163+ 巨噬细胞增多。然而，CD163+巨噬细胞的双重免疫荧光研究显示，DLE 皮肤中存在 M1（CXCL10、肿瘤坏死因子-α 和 CD127）和 M2（CD209 和转化生长因子-β）巨噬细胞相关蛋白的少量共表达。尽管 CD163+ 巨噬细胞的子集在 DLE 皮肤中表现出混合极化，但其他免疫细胞（例如 T 细胞）可以促进这些巨噬细胞相关基因的表达。本文的在线版本 (doi:10.1186/s13075-015-0839-3) 包含补充材料，可供授权用户使用。
Lesional skin of patients with discoid lupus erythematosus (DLE) contains macrophages, whose polarization has yet to be investigated. To test our hypothesis that M1 macrophages would be increased in DLE skin, we examined transcriptome alterations in immune cell gene expression and macrophage features in DLE and normal skin by using gene expression and histochemical approaches. Gene expression of RNA from DLE lesional and normal control skin was compared by microarrays and quantitative real-time polymerase chain reaction (RT-PCR). Both skin groups were analyzed for CD163 expression by immunohistochemistry. Double immunofluorescence studies were performed to characterize protein expression of CD163+ macrophages. DLE skin had twice as many upregulated genes than downregulated genes compared with normal skin. Gene set enrichment analysis comparing differentially expressed genes in DLE and normal skin with previously published gene sets associated with M1 and M2 macrophages showed strong overlap between upregulated genes in DLE skin and M1 macrophages. Quantitative RT-PCR showed that several M1 macrophage-associated genes—e.g., chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 5 (CCL5), and signal transducer and activator of transcription 1 (STAT1)—had amplified mRNA levels in DLE skin. CD163+ macrophages were increased near the epidermal-dermal junction and perivascular areas in DLE skin compared with normal skin. However, double immunofluorescence studies of CD163+ macrophages revealed minor co-expression of M1 (CXCL10, tumor necrosis factor-alpha, and CD127) and M2 (CD209 and transforming growth factor-beta) macrophage-related proteins in DLE skin. Whereas a subset of CD163+ macrophages displays mixed polarizations in DLE skin, other immune cells such as T cells can contribute to the expression of these macrophage-related genes. The online version of this article (doi:10.1186/s13075-015-0839-3) contains supplementary material, which is available to authorized users.