Polymorphonuclear myeloid-derived suppressor cells inhibit natural killer cell function in neuromyelitis optica spectrum disorder via the CD155-TIGIT axis.

Natural killer (NK) cells and myeloid-derived suppressor cells (MDSCs) are implicated in neuromyelitis optica spectrum disorder (NMOSD), but their potential interplay remains unclear. In this study, we identified an increased frequency of polymorphonuclear MDSCs (PMN-MDSCs) and a decreased frequency of NK cells in NMOSD patients. In patients during remission, CD155 expression on PMN-MDSCs and TIGIT expression on NK cells were elevated, while NK cell activating receptors NKp30 and NKp46 were downregulated. The Expanded Disability Status Scale score correlated positively with MDSC and NKp46+ NK cell frequencies, but negatively with TIGIT+ NK cells. In vitro, PMN-MDSCs suppressed NK cell function through both soluble mediators and the contact-dependent CD155/TIGIT axis, as evidenced by reduced IFN-γ secretion and receptor modulation. This suppression was reversed by blocking CD155 or TIGIT. These findings suggest that PMN-MDSCs could inhibit NK cell function in NMOSD potentially via the CD155/TIGIT axis.