单核细胞稳定素-1抑制Th1淋巴细胞的激活。

Monocyte Stabilin-1 Suppresses the Activation of Th1 Lymphocytes.

作者信息

Palani Senthil, Elima Kati, Ekholm Eeva, Jalkanen Sirpa, Salmi Marko

机构信息

MediCity Research Laboratory, University of Turku, Turku 20520, Finland; Turku Doctoral Programme of Molecular Medicine, University of Turku, Turku 20520, Finland; Turku Doctoral Programme of Biomedical Sciences, University of Turku, Turku 20520, Finland;

MediCity Research Laboratory, University of Turku, Turku 20520, Finland; Department of Medical Biochemistry and Genetics, University of Turku, Turku 20520, Finland;

出版信息

J Immunol. 2016 Jan 1;196(1):115-23. doi: 10.4049/jimmunol.1500257. Epub 2015 Nov 25.

DOI:10.4049/jimmunol.1500257

PMID:26608916

Abstract

In this study, we analyzed the putative functions of stabilin-1 in blood monocytes. Microarray analysis revealed downregulation of several proinflammatory genes in the stabilin-1(high) monocytes when compared with stabilin-1(low) monocytes. When cocultured with stabilin-1(high) monocytes, IFN-γ synthesis by T cells was diminished in Ag-recall assays. Knockdown of stabilin-1 in monocytes increased the synthesis of several proinflammatory molecules, including TNF-α, and supported high IFN-γ and low IL-4 and IL-5 production by T cells in Ag-specific stimulation assays. Anti-stabilin-1 Ab treatment also led to increased IFN-γ synthesis in the recall assays. In clinical settings, the expression of stabilin-1 was diminished on blood monocytes and tissue macrophages under proinflammatory conditions. These data define stabilin-1 as a new immunosuppressive molecule and suggest that stabilin-1(high) monocytes may dampen proinflammatory reactions in vivo.

摘要

在本研究中，我们分析了稳定素-1在血液单核细胞中的假定功能。微阵列分析显示，与稳定素-1（低表达）单核细胞相比，稳定素-1（高表达）单核细胞中几种促炎基因的表达下调。在抗原回忆试验中，当与稳定素-1（高表达）单核细胞共培养时，T细胞的IFN-γ合成减少。单核细胞中稳定素-1的敲低增加了几种促炎分子的合成，包括TNF-α，并在抗原特异性刺激试验中支持T细胞产生高IFN-γ以及低IL-4和IL-5。抗稳定素-1抗体处理在回忆试验中也导致IFN-γ合成增加。在临床环境中，在促炎条件下，血液单核细胞和组织巨噬细胞上稳定素-1的表达减少。这些数据将稳定素-1定义为一种新的免疫抑制分子，并表明稳定素-1（高表达）单核细胞可能在体内抑制促炎反应。