Modulation of NCX1 expression in monocytes associates with multiple sclerosis progression

Ionic imbalance and functional heterogeneity of monocytes play key roles in multiple sclerosis (MS) progression. A better understanding of monocyte response in the context of ionic dysregulation during MS course may have relevant implications for understanding of disease pathogenesis and treatments. The sodium calcium exchanger NCX1 influences monocyte-derived macrophages reactivity under inflammation; however, little is known about its monocyte-specific expression during MS course. By means of RT-PCR, flow cytometry, and confocal analyses, we determined the expression profiling of NCX1 exchanger in monocytes of patients during relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) course. NCX1 expression was significantly upregulated in monocytes from transitional RRMS subjects. Conversely, it was significantly reduced in all monocyte subsets after RRMS conversion to SPMS. Interestingly, NCX1 levels in monocytes significantly correlated with the percentage and growth ability of the regulatory T cell (Treg) subset, whose derangement underlies MS progression. Perturbation of transcripts encoding the Ca²⁺-ATPase isoform 1 and 4, the Na⁺/K⁺-ATPase α1 subunit, and the long non-coding RNA SLC8A1-AS1 associated with NCX1 changes in peripheral blood mononuclear cells (PBMC) during MS. Our findings demonstrated a stage-specific dysregulation of NCX1 exchanger in monocytes during MS progression and suggested that ionic imbalance in monocytes may influence not only their functional response but also the immune regulatory network during MS course. These data may be relevant for the identification of novel biomarkers and/or therapeutic targets in MS.