The role of PD-1 and Tim-3 in regulating the suppressive activity of myeloid-derived suppressor cells in axial spondyloarthritis: association with clinical and laboratory parameters.

Monocytic myeloid-derived suppressor cells (M-MDSCs) expand in axial spondyloarthritis (axSpA), although their pathogenetic role and functional state are still unclear. The aim of this study was to investigate checkpoint receptors PD-1/Tim-3 expression on M-MDSCs in axSpA, assessing their relationship with clinical disease parameters and M-MDSC suppressor potential. The study included 19 healthy donors and 32 axSpA patients. As markers of the suppressor potential of M-MDSCs, suppressor molecules arginase 1 (Arg-1) and tyrosine kinase Mer (MerTK) were evaluated. M-MDSC count and their expression of PD-1, Tim-3, Arg-1, and MerTK were evaluated using flow cytometry. M-MDSC frequency directly correlated with the level of C-reactive protein, whereas PD-1 expression on M-MDSCs inversely correlated with the erythrocyte sedimentation rate. Thus, high axSpA activity was associated with an increased M-MDSC content with unchanged PD-1 expression, whereas low activity was linked to an increased PD-1 expression without changing M-MDSC frequency. Additionally, the PD-1+ M-MDSC count directly correlated with the percentage of MerTK+ M-MDSCs. Tim-3 showed no correlation with the clinical disease parameters; however, an inverse correlation was observed between Tim-3 and Arg-1 expression in M-MDSCs. In turn, the Arg-1+ M-MDSCs count in patients receiving non-steroidal anti-inflammatory drugs and having higher disease activity was reduced, while in the patient group receiving tumor necrosis factor alpha-inhibitors and having lower activity, it was increased. The obtained results may indicate a positive role of PD-1 in preventing inflammation in axSpA, whereas Tim-3 presumably weakens the anti-inflammatory M-MDSC potential in axSpA.