Syncytin-1/HERV-W envelope is an early activation marker of leukocytes and is upregulated in multiple sclerosis patients.,European Journal of Immunology

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Syncytin-1/HERV-W envelope is an early activation marker of leukocytes and is upregulated in multiple sclerosis patients.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-02-11 , DOI: 10.1002/eji.201948423
Marta Garcia-Montojo _{1,

2} , Eulalia Rodriguez-Martin ₁ , Priscila Ramos-Mozo ₃ , Isabel Ortega-Madueño ₂ , Maria Inmaculada Dominguez-Mozo ₂ , Ana Arias-Leal ₂ , Maria Ángel García-Martínez ₃ , Ignacio Casanova ₂ , Victoria Galan ₂ , Rafael Arroyo ₂ , Roberto Álvarez-Lafuente ₂ , Luisa María Villar ₁

Affiliation

Syncytin-1 is the envelope protein of the human endogenous retrovirus W (HERV-W). It has been related to multiple sclerosis (MS) but its role in cellular immunity and its pathogenic mechanism in the autoimmune context are not fully understood. We analyzed syncytin-1 levels in peripheral blood mononuclear cells (PBMC) subsets from healthy donors, MS patients in relapse or remission, and patients with acute infections by flow cytometry. PBMC cultures were also prepared to analyze protein expression kinetics. MS patients had higher levels of syncytin-1 levels than controls. We found that syncytin-1 is elevated in monocytes during MS relapses and infections. Cells expressing syncytin-1, including monocytes, T and B lymphocytes, and NKs presented mainly an activated phenotype and, upon stimulation with LPS, its levels increased rapidly on antigen-presenting cells. Syncytin-1 ligation promoted the activation of monocytes, as demonstrated by the upregulation of CD80 and the nonclassical subset CD14low CD16+ . Our results suggest an important role for syncytin-1 in the activation of leukocytes. Given that the expression of syncytin-1 is upregulated in MS patients, this protein might be contributing to the autoimmune cascade in the disease.

中文翻译：

Syncytin-1 / HERV-W包膜是白细胞的早期激活标记，在多发性硬化症患者中被上调。

Syncytin-1是人类内源性逆转录病毒W（HERV-W）的包膜蛋白。它与多发性硬化症（MS）有关，但在自身免疫背景下其在细胞免疫中的作用及其致病机理尚未完全了解。我们通过流式细胞仪分析了健康供体，复发或缓解的MS患者以及患有急性感染的患者的外周血单个核细胞（PBMC）亚群中的syncytin-1水平。还准备了PBMC培养物以分析蛋白质表达动力学。MS患者的syncytin-1水平高于对照组。我们发现在MS复发和感染过程中单核细胞中syncytin-1升高。表达syncytin-1的细胞（包括单核细胞，T和B淋巴细胞以及NK）主要表现出激活的表型，并且在LPS刺激下，其水平在抗原呈递细胞上迅速增加。Syncytin-1的连接促进了单核细胞的活化，这通过CD80和非经典CD14low CD16 +的上调来证明。我们的结果表明，合胞素1在白细胞激活中起着重要作用。鉴于在MS患者中syncytin-1的表达上调，该蛋白可能有助于疾病中的自身免疫级联反应。

更新日期：2020-02-11

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