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国际联合团队发现多发性硬化症的治疗靶标
来源:小柯机器人 发布时间:2019/8/12 14:47:02

近日,由瑞士苏黎世大学Burkhard Becher教授牵头组织的国际联合团队的研究显示,GM-CSF和CXCR4定义了多发性硬化症(multiple sclerosis,MS)中的T辅助细胞特征(T helper cell signature)。 相关论文于2019年8月发表在国际顶尖学术期刊《自然—医学》上。

研究团队通过高维单细胞质量流式细胞仪(CyTOF)来确定复发缓解型多发性硬化症(RRMS)患者的特征性细胞和细胞因子极化谱。结合基于神经网络的表征学习算法,在MS患者中鉴定出扩增的T辅助细胞亚群,其特征在于粒细胞 - 巨噬细胞集落刺激因子和CXC趋化因子受体4型的表达。该细胞特征在于,包括在外周血中表达的晚期抗原4,也在患有复发缓解型多发性硬化症的患者的中枢神经系统中表达富集。独立队列研究证实,与其他炎症和非炎症病症相比,多发性硬化症患者的这种细胞群增加。论文最后指出,在有效的疾病改善疗法下患病群体数量减少了,这进一步表明了新鉴定的T细胞谱可作为多发性硬化症中特定治疗靶标。

据悉,细胞因子失调是慢性炎症性疾病如多发性硬化症的主要驱动因素。

附:英文原文

Title: GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis

Author: Edoardo Galli, Felix J. Hartmann, Bettina Schreiner, Florian Ingelfinger, Eirini Arvaniti, Martin Diebold, Dunja Mrdjen, Franziska van der Meer, Carsten Krieg, Faiez Al Nimer, Nicholas Sanderson, Christine Stadelmann, Mohsen Khademi, Fredrik Piehl, Manfred Claassen, Tobias Derfuss, Tomas Olsson, Burkhard Becher

Issue&Volume: Volume 25 Issue 8, August 2019

Abstract: Cytokine dysregulation is a central driver of chronic inflammatory diseases such as multiple sclerosis (MS). Here, we sought to determine the characteristic cellular and cytokine polarization profile in patients with relapsingremitting multiple sclerosis (RRMS) by high-dimensional single-cell mass cytometry (CyTOF). Using a combination of neural network-based representation learning algorithms, we identified an expanded T helper cell subset in patients with MS, characterized by the expression of granulocytemacrophage colony-stimulating factor and the C-X-C chemokine receptor type 4. This cellular signature, which includes expression of very late antigen 4 in peripheral blood, was also enriched in the central nervous system of patients with relapsingremitting multiple sclerosis. In independent validation cohorts, we confirmed that this cell population is increased in patients with MS compared with other inflammatory and non-inflammatory conditions. Lastly, we also found the population to be reduced under effective disease-modifying therapy, suggesting that the identified T cell profile represents a specific therapeutic target in MS.

DOI: 10.1038/s41591-019-0521-4

Source:https://www.nature.com/articles/s41591-019-0521-4

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章:《自然—医学》:Volume 25 Issue 8