期刊
NATURE MEDICINE
卷 25, 期 8, 页码 1290-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-019-0521-4
关键词
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资金
- Swiss National Science Foundation [310030_170320, 316030_150768, CRSII5_183478]
- European Union
- Swiss Multiple Sclerosis Society
- Van Riemsdijk PhD fellowship
- Swiss National Science Foundation (SNF) [316030_150768, CRSII5_183478, 310030_170320] Funding Source: Swiss National Science Foundation (SNF)
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.
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