Mathes Allison L, Christmann Romy B, Stifano Giuseppina, Affandi Alsya J, Radstake Timothy R D J, Farina G Alessandra, Padilla Cristina, McLaughlin Sarah, Lafyatis Robert
Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Ann Rheum Dis. 2014 Oct;73(10):1864-72. doi: 10.1136/annrheumdis-2012-202814. Epub 2013 Jul 19.
To characterise global chemokine expression in systemic sclerosis (SSc) skin in order to better understand the relationship between chemokine expression and vascular inflammation in this disease.
We investigated chemokine mRNA expression in the skin through quantitative PCR analysis comparing patients with diffuse cutaneous (dcSSc) or limited cutaneous (lcSSc) disease with healthy controls. We tested correlations between the most regulated chemokines and vascular inflammation and macrophage recruitment. CCL19 expression was examined in human primary immune cells treated with innate immune activators.
The chemokines, CCL18, CCL19 and CXCL13, were upregulated in dcSSc skin, and CCL18 in lcSSc skin. Expression of CCL19 in dcSSc skin correlated with markers of vascular inflammation and macrophage recruitment. Immunofluorescence data showed CCL19 colocalisation with CD163 macrophages in dcSSc skin. In vitro studies on human primary cells demonstrated that CCL19 expression was induced after toll-like receptor activation of peripheral blood mononuclear cells and separated populations of CD14 monocytes.
CCL18, CCL19 and CXCL13-chemoattractants for macrophage and T cell recruitment-were three of six chemokines with the highest expression in dcSSc skin. Increased CCL19 expression in the skin suggests a role for CCL19 in the recruitment of immune cells to the peripheral tissue. Induction of CCL19 in macrophages but not structural cells indicates a role for skin-resident or recruited immune cells in perivascular inflammation. This study demonstrates that CCL19 is a sensitive marker for the perivascular inflammation and immune cell recruitment seen in dcSSc skin disease.
对系统性硬化症（SSc）皮肤中的整体趋化因子表达进行特征分析，以便更好地理解趋化因子表达与该疾病血管炎症之间的关系。
我们通过定量PCR分析，比较弥漫性皮肤型（dcSSc）或局限性皮肤型（lcSSc）疾病患者与健康对照者皮肤中趋化因子mRNA的表达。我们测试了调控最为明显的趋化因子与血管炎症及巨噬细胞募集之间的相关性。对用天然免疫激活剂处理的人原代免疫细胞中的CCL19表达进行了检测。
趋化因子CCL18、CCL19和CXCL13在dcSSc皮肤中上调，CCL18在lcSSc皮肤中上调。dcSSc皮肤中CCL19的表达与血管炎症及巨噬细胞募集的标志物相关。免疫荧光数据显示，在dcSSc皮肤中CCL19与CD163巨噬细胞共定位。对人原代细胞的体外研究表明，外周血单核细胞和分离出的CD14单核细胞群体经Toll样受体激活后可诱导CCL19表达。
CCL18、CCL19和CXCL13（巨噬细胞和T细胞募集的趋化因子）是dcSSc皮肤中表达最高的六种趋化因子中的三种。皮肤中CCL19表达增加表明CCL19在免疫细胞募集至外周组织中发挥作用。巨噬细胞而非结构细胞中CCL19的诱导表明皮肤驻留或募集的免疫细胞在血管周围炎症中发挥作用。本研究表明CCL19是dcSSc皮肤疾病中血管周围炎症和免疫细胞募集的敏感标志物。
