14:30-14:40 Regulatory T-cells undergo apoptosis during preeclampsia prevented by Gal-2
Journal of Reproductive Immunology(2023)
摘要
Preeclampsia (PE) is a severe pregnancy disorder with no known curative therapy. There are several open questions to be answered regarding the pathophysiology of the development of PE. Numerous factors are involved in its genesis, like defective placentation, vascular impairment, and an altered immune response. The activation of the adaptive and innate immune system represents an immunologic particularity during PE. Proinflammatory cytokines are predominantly produced whereas immune regulatory and immune suppressive factors are diminished in PE. In the present study we focused on the recruitment of regulatory T-cells (Tregs) which are key players in processes mediating immune tolerance. To identify Tregs in the decidua, an immunohistochemical staining of FoxP3 of 32 PE and 34 control placentas was performed. Furthermore an immunohistochemical staining of CCL22, a cytokine that recruits Tregs, was conducted. To analyze the potential apoptosis behavior of Tregs in PE, the control and PE placentas were additionally stained by TUNEL (TdT-mediated dUTP-biotin nick end labeling) and FoxP3 double staining. In addition, the apoptosis rate of isolated Tregs was measured after incubation with galectin-2 following induction of apoptosis by FasL. Quantitative survey of apoptotic Tregs was performed by a caspase 3 ELISA from R&D Systems. A clearly reduced number of FoxP3 positive cells in the decidua of preeclamptic women could be shown in our analysis (p = 0.036). Furthermore, CCL22, a well-known Treg chemoattractant, was immunohistochemically evaluated. Interestingly, CCL22 expression was increased at the maternal-fetal interface in PE affected pregnancies (psyncytiotrophoblast = 0.035, pdecidua = 0.004). Therefore, the hypothesis that Tregs undergo apoptosis at the materno-fetal interface during PE was generated, and verified by a FoxP3 / TUNEL staining. Galectin-2 (Gal-2), a member of the family of carbohydrate-binding proteins, which is known to be downregulated during PE, seems to play a pivotal role in T-cell apoptosis. By performing a cell culture experiment with isolated Tregs, we could identify Gal-2, as a factor which seems to prevent apoptosis of Tregs. Our findings point to a cascade of apoptosis of Tregs at the materno-fetal interface during PE. Gal-2 might be a potential therapeutic target in PE to regulate immune tolerance.
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关键词
preeclampsia,apoptosis,t-cells
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