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<p>The absence of maternal immune rejection of a haploidentical fetus remains unexplained. We hypothesize that the presence of different HLA antigens on trophoblasts and maternal cells via killer cell immunoglobulin-like receptors (KIRs) provides two-way tuning (education, licensing) of decidual natural killer cells (dNK) with the appearance of alloreactive (HvG) and autoreactive (HvH) dNK. Disturbances in dNK<sub>HvG</sub> and dNK<sub>HvH</sub> representation may lead to abnormalities in placental development and pregnancy pathology. Our data show that recurrent pregnancy loss is not associated with specific HLA and KIR genotypes in mother and fetus, although the peculiarities of tuning involving KIR3DL2 may affect pregnancy outcome. Mathematical modeling shows the dependence of dNK<sub>HvG</sub> and dNK<sub>HvH</sub> representation on the probability of random KIR gene expression. The new description of NK cell involvement in the immune response in the placenta via two-way tuning is applicable to all cases where there are target cells with normal and different “guest” HLA expression (viral infections, tumors).</p>

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Two-way tuning of the decidual natural killer cells and recurrent pregnancy loss

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Sergey Petrovich Krechetov,
  • Olga Vladimirovna Khoroshkeeva,
  • Tatyana Eduardovna Yankevich,
  • Yuri Valentinovich Shirokov,
  • Pavel Igorevich Borovikov,
  • Liubov Valentinovna Krechetova,
  • Nana Kartlosovna Tetruashvili,
  • Dmitry Yurievich Trofimov,
  • Gennady Tikhonovich Sukhikh

摘要

The absence of maternal immune rejection of a haploidentical fetus remains unexplained. We hypothesize that the presence of different HLA antigens on trophoblasts and maternal cells via killer cell immunoglobulin-like receptors (KIRs) provides two-way tuning (education, licensing) of decidual natural killer cells (dNK) with the appearance of alloreactive (HvG) and autoreactive (HvH) dNK. Disturbances in dNKHvG and dNKHvH representation may lead to abnormalities in placental development and pregnancy pathology. Our data show that recurrent pregnancy loss is not associated with specific HLA and KIR genotypes in mother and fetus, although the peculiarities of tuning involving KIR3DL2 may affect pregnancy outcome. Mathematical modeling shows the dependence of dNKHvG and dNKHvH representation on the probability of random KIR gene expression. The new description of NK cell involvement in the immune response in the placenta via two-way tuning is applicable to all cases where there are target cells with normal and different “guest” HLA expression (viral infections, tumors).