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基于单细胞 RNA 测序的复发性缓解型多发性硬化症患者 PBMCs 中 VISTA 的表达模式:一项单细胞 RNA 测序研究。

The expression pattern of VISTA in the PBMCs of relapsing-remitting multiple sclerosis patients: A single-cell RNA sequencing-based study.

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Biomed Pharmacother. 2022 Apr;148:112725. doi: 10.1016/j.biopha.2022.112725. Epub 2022 Feb 17.

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Dysregulated immune responses have been implicated in MS development. Growing evidence has indicated that inhibitory immune checkpoint molecules can substantially regulate immune responses and maintain immune tolerance. V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule that can suppress immune responses; however, its expression pattern in the peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) has not thoroughly been studied. Herein, we evaluated Vsir expression in PBMCs of RRMS patients and characterized the expression pattern of the Vsir in the PBMCs of MS patients. Besides, we investigated the effect of fingolimod, IFNβ-1α, glatiramer acetate (GA), and dimethyl fumarate (DMF) on Vsir expression in PBMCs of RRMS patients. Our results have shown that Vsir expression is significantly downregulated in the PBMCs of patients with RRMS. Besides, the single-cell RNA sequencing results have demonstrated that Vsir expression is downregulated in classical monocyte, intermediate monocytes, non-classical monocytes, myeloid DCs (mDC), Plasmacytoid dendritic cells (pDCs), and naive B-cells of PBMCs of MS patients compared to the control. In addition, DMF, IFNβ-1α, and GA have significantly upregulated Vsir expression in the PBMCs of RRMS patients. Collectively, the current study has shed light on Vsir expression in the PBMCs of MS patients; however, further studies are needed to elucidate the significance of VISTA in the mentioned immune cells.

摘要

多发性硬化症(MS)是一种中枢神经系统(CNS)的炎症性疾病。失调的免疫反应被认为与 MS 的发展有关。越来越多的证据表明,抑制性免疫检查点分子可以显著调节免疫反应并维持免疫耐受。T 细胞激活的 V 域免疫球蛋白抑制剂(VISTA)是一种新型的抑制性免疫检查点分子,可抑制免疫反应;然而,其在外周血单核细胞(PBMC)中的表达模式在复发缓解型多发性硬化症(RRMS)患者中尚未得到充分研究。在此,我们评估了 RRMS 患者 PBMC 中的 Vsir 表达,并对 MS 患者 PBMC 中 Vsir 的表达模式进行了表征。此外,我们研究了芬戈莫德、IFNβ-1α、那他珠单抗和富马酸二甲酯对 RRMS 患者 PBMC 中 Vsir 表达的影响。我们的结果表明,RRMS 患者 PBMC 中的 Vsir 表达显著下调。此外,单细胞 RNA 测序结果表明,与对照组相比,MS 患者 PBMC 中的经典单核细胞、中间单核细胞、非经典单核细胞、髓样树突状细胞(mDC)、浆细胞样树突状细胞(pDC)和幼稚 B 细胞中 Vsir 表达下调。此外,DMF、IFNβ-1α 和 GA 可显著上调 RRMS 患者 PBMC 中的 Vsir 表达。总之,本研究揭示了 MS 患者 PBMC 中 Vsir 的表达;然而,需要进一步的研究来阐明 VISTA 在上述免疫细胞中的意义。

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