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 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 MS patients, characterized by the expression of GM-CSF and the C-X-C chemokine receptor type 4. This cellular signature, which includes expression of very late antigen 4 (VLA4) in peripheral blood, was also enriched in the central nervous system of RRMS patients. In independent validation cohorts, we confirmed that this cell population is increased in MS patients compared to 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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