Tyshchuk Elizaveta, Denisova Elizaveta, Grebenkina Polina, Pereviazkina Marina, Stolbovaya Anastasia, Smirnov Ilya, Shashkova Olga, Gryazeva Irina, Terekhina Lidiya, Sokolov Dmitry
Federal State Budgetary Scientific Institution, Research Institute of Obstetrics, Gynecology and Reproductology Named After D.O. Ott, 199034 St. Petersburg, Russia.
Saint-Petersburg Pasteur Institute, 197101 St. Petersburg, Russia.
Int J Mol Sci. 2025 Aug 29;26(17):8400. doi: 10.3390/ijms26178400.
MICA/B molecules (MICs) are stress-induced molecules expressed by infected and tumor cells. Their expression also characterizes trophoblast cells. Cytotoxic lymphocytes, including natural killer (NK) cells, express the NKG2D receptor, aiding them in the recognition and destruction of target cells that present MICs. To evade destruction, target cells employ various defense mechanisms, including the secretion of soluble forms of MICs. Choriocarcinoma JEG-3 cells and NK-92 cells were used to assess the expression of MICs and NKG2D. The cytotoxicity of NK-92 cells against JEG-3 cells in the presence of trichostatin A (TSA), anti-MICA/B antibodies (anti-MICA/B), and recombinant MIC proteins (rMICA/B) was evaluated. JEG-3 cells and NK-92 cells express MICs. Additionally, NK-92 cells exhibit high levels of NKG2D receptor expression. TSA treatment reduced the surface expression of MICs on choriocarcinoma cells, and was also associated with the release of soluble MICB. However, the TSA-induced decrease in MIC expression by choriocarcinoma cells did not protect them from the cytotoxic effects of NK cells. Only the activation of NK cells by IL-12 resulted in a decline in susceptibility of TSA-treated choriocarcinoma cells to NK cell-mediated cytotoxicity. Thus, NK cells activated by IL-12 lose their ability to effectively kill TSA-treated choriocarcinoma cells through the MIC-mediated mechanisms.
MICA/B分子（MICs）是由受感染细胞和肿瘤细胞表达的应激诱导分子。它们的表达也是滋养层细胞的特征。包括自然杀伤（NK）细胞在内的细胞毒性淋巴细胞表达NKG2D受体，有助于它们识别和破坏呈递MICs的靶细胞。为了逃避破坏，靶细胞采用各种防御机制，包括分泌可溶性形式的MICs。使用绒癌JEG-3细胞和NK-92细胞来评估MICs和NKG2D的表达。评估了曲古抑菌素A（TSA）、抗MICA/B抗体（抗MICA/B）和重组MIC蛋白（rMICA/B）存在下NK-92细胞对JEG-3细胞的细胞毒性。JEG-3细胞和NK-92细胞表达MICs。此外，NK-92细胞表现出高水平的NKG2D受体表达。TSA处理降低了绒癌细胞上MICs的表面表达，并且还与可溶性MICB的释放有关。然而，TSA诱导的绒癌细胞MIC表达降低并未保护它们免受NK细胞的细胞毒性作用。只有IL-12激活NK细胞才导致TSA处理的绒癌细胞对NK细胞介导的细胞毒性的敏感性下降。因此，IL-12激活的NK细胞通过MIC介导的机制失去了有效杀伤TSA处理的绒癌细胞的能力。
