GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis
GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis
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DOI：
10.1038/s41591-019-0521-4
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发表时间：
2019-08-01
期刊：
影响因子：
82.9
通讯作者：
Becher, Burkhard
中科院分区：
文献类型：
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作者：
Galli, Edoardo;Hartmann, Felix J.;Becher, Burkhard
细胞因子失调是慢性炎性疾病如多发性硬化症（MS）的中心驱动因素。在这里，我们试图通过高维单细胞质谱（CyTOF）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。使用基于神经网络的表征学习算法的组合，我们确定了MS患者的扩展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C-X-C趋化因子受体4型的表达。这种细胞特征，包括外周血中极晚期抗原4的表达，也在复发缓解型多发性硬化症患者的中枢神经系统中富集。在独立的验证队列中，我们证实了与其他炎症和非炎症条件相比，MS患者的这种细胞群增加。最后，我们还发现，在有效的疾病修饰治疗下，该群体减少，这表明所鉴定的T细胞谱代表了MS中的特定治疗靶点。
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 relapsing-remitting 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 granulocyte-macrophage 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 relapsing-remitting 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.