Increased expression of Mer tyrosine kinase in circulating dendritic cells and monocytes of lupus patients: correlations with plasma interferon activity and steroid therapy.

Increased expression of Mer tyrosine kinase in circulating dendritic cells and monocytes of lupus patients: correlations with plasma interferon activity and steroid therapy.
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狼疮患者的循环树突状细胞和单核细胞中Mer酪氨酸激酶的表达增加:与血浆干扰素活性和类固醇治疗的相关性。

DOI:
10.1186/ar4517
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发表时间:
2014-03-21
影响因子:
4.9
通讯作者:
Cohen PL
Cohen PL
中科院分区:
医学2区
文献类型:
--
作者:
Hilliard BA;Zizzo G;Ulas M;Linan MK;Schreiter J;Cohen PL

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免疫调节Mer酪氨酸激酶(Mer)的最佳去除凋亡细胞的要求促使我们看看它在系统性红斑狼疮(SLE),其中凋亡细胞清除异常的表达。我们比较了Mer在正常人和SLE患者中的表达水平。我们采用流式细胞术分离外周血单个核细胞比较白细胞亚群上的Mer水平。我们使用Mer特异性酶联免疫吸附试验(ELISA)来定量血浆中的可溶性Mer(sMer)。来自正常个体和来自SLE患者的单核细胞、CD 1c+髓样树突状细胞(mDC)和浆细胞样树突状细胞(pDC)表达Mer。在正常人和SLE患者中,CD 14 ++ CD 16+单核细胞亚群表达最高水平的Mer,而CD 14 intCD 16+单核细胞亚群表达水平略低。与对照组相比,SLE患者CD 1c + mDCs和pDCs表面Mer水平及血中sMer水平均升高。在患者中,CD 14 intCD 16+、CD 14 ++ CD 16-单核细胞和CD 1c+树突状细胞上的Mer水平与血液中检测到的I型干扰素(IFN-I)活性呈正相关。在接受激素治疗的SLE患者中,单核细胞Mer表达与泼尼松剂量相关,泼尼松治疗组CD 1c+髓系树突状细胞Mer表达水平高于未接受激素治疗组。我们没有发现狼疮血液中Mer表达的整体缺陷。相反,我们观察到DC群体中Mer表达水平增加,这可能代表SLE患者对IFN-1增加的反应。皮质类固醇诱导的Mer表达增强可能有助于其在SLE中的有益作用。
The requirement for the immunoregulatory Mer tyrosine kinase (Mer) for optimal removal of apoptotic cells prompted us to look at its expression in systemic lupus erythematosus (SLE), in which apoptotic cell clearance is abnormal. We compared the levels of expression of Mer in normal human subjects and in patients with SLE. We used flow cytometry of isolated peripheral blood mononuclear cells to compare the levels of Mer on leukocyte subsets. We used a Mer-specific enzyme-linked immunosorbent assay (ELISA) to quantify soluble Mer (sMer) in plasmas. Monocytes, CD1c+ myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from both normal individuals and from SLE patients expressed Mer. In both normal and SLE patients, the CD14++CD16+ subpopulation of monocytes expressed the highest levels of Mer, with somewhat lower levels on the CD14intCD16+ population. Mer levels on CD1c+ mDCs and pDCs, and sMer levels in blood were increased in SLE patients compared with controls. In patients, Mer levels on CD14intCD16+, CD14++CD16- monocytes, and CD1c+ dendritic cells correlated positively with type I interferon (IFN-I) activity detected in blood. In SLE patients treated with corticosteroids, Mer expression on monocytes correlated with prednisone dose, CD1c+ myeloid dendritic cells in patients treated with prednisone had higher levels of Mer expression than those in patients not receiving prednisone. We found no global defect in Mer expression in lupus blood. In contrast, we observed increased levels of Mer expression in DC populations, which could represent a response to increased IFN-I in SLE patients. Enhanced Mer expression induced by corticosteroids may contribute to its beneficial effects in SLE.
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