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<p>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<sup>+</sup> M-MDSC count directly correlated with the percentage of MerTK<sup>+</sup> 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<sup>+</sup> 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.</p>

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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

  • 期刊论文

  • 发表日期：

    2026年4月1日

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  • Tamara Viktorovna Tyrinova,
  • Ludmila Vasilievna Sakhno,
  • Ivan Vladimirovich Savkin,
  • Ekaterina Jakovlevna Shevela,
  • Marina Aleksandrovna Tikhonova,
  • Anastasiia Yurievna Morenkova,
  • Nadezhda Aleksandrovna Ilina,
  • Oksana Aleksandrovna Chumasova,
  • Nadezhda Sergeevna Shkaruba,
  • Anastasia Valerievna Fedorova,
  • Yulia Dmitrievna Kurochkina,
  • Vitaly Olegovich Omelchenko,
  • Elena Alekseevna Letyagina,
  • Maxim Aleksandrovich Korolev,
  • Aleksey Eduardovich Sizikov,
  • Elena Removna Chernykh

摘要

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.