The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia—A Narrative Review

Mittelberger, Johanna; Seefried, Marina; Franitza, M; Garrido, F; Ditsch, Nina; Jeschke, Udo; Dannecker, Christian

doi:10.3390/medicina58020157

Cited by 16 publications

(11 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…was consistent with a previous study 39 . The PD‐1/PD‐L1 system may be altered in PE to augment the immune response even though the mechanism is not well understood 40 . In one previous study, while there was an increased expression of B7‐H1 on NKT‐like cells in early‐onset PE, suggestive of the involvement of the PD‐1/PD‐L1 axis in early‐onset PE, no significant change in the soluble or free form of B7‐H1 was found.…”

Section: Discussionsupporting

confidence: 92%

“…Studies have shown that there is a significant reduction in the function of T regulatory cells (Tregs) and an increased expression of PD‐1 on exhausted Tregs in PE. The presence of PD‐1 on exhausted Tregs may indicate that PD‐1 expression on Tregs may lead to function reduction which may contribute to PE 40 …”

Section: Discussionmentioning

confidence: 99%

“…The presence of PD-1 on exhausted Tregs may indicate that PD-1 expression on Tregs may lead to function reduction which may contribute to PE. 40 When assessed for predictive ability, TNF-α was the most predictive, while IL-6 was the least predictive of PE. However, none had a better diagnostic potential as all the AUCs were less than 0.65.…”

Section: Predicting Pe With Cytokines and B7 Moleculesmentioning

confidence: 99%

See 2 more Smart Citations

Immune checkpoint molecules B7‐1 and B7‐H1 as predictive markers of pre‐eclampsia: A case–control study in a Ghana

Akilla,

Nchor,

Banyeh

et al. 2024

Immunity Inflam & Disease

View full text Add to dashboard Cite

Background/AimImmune tolerance in the fetal–maternal junction is maintained by a balance in the Th1/Th2 system. Th1‐type immunity is associated with pro‐inflammatory cytokines and immune checkpoint molecules (ICMs) such as B7‐H1, while Th2‐type immunity is characterized by anti‐inflammatory cytokines and ICMs such as B7‐1. Any imbalance in the Th1/Th2 immune system may lead to adverse pregnancy outcomes such as pre‐eclampsia (PE). Hitherto, the potential of serum B7‐1 and B7‐H1 proteins as early markers of PE has not been explored in the Ghanaian population.Materials and MethodsThis was a case–control study from May 2020 to April 2022 at the War Memorial and the Upper East Regional Hospitals. The study involved 291 women, including 180 (61.9%) with normotensive pregnancy and 111 (38.1%) with PE. Venous blood samples were collected and assayed for blood cell count, serum interleukins (ILs)‐4, ‐6, ‐12, ‐18, and TNF‐α as well as serum B7‐1 and B7‐H1 proteins.ResultsThe monocyte count (p = .007), the serum levels of IL‐18 (p = .035), TNF‐α (p = .001), and B7‐H1 (p = .006) were significantly higher in PE than in normotensive pregnancy. In addition, the monocyte count (p = .002), the serum levels of IL‐12 (p = .029), TNF‐α (p = .016), and B7‐1 (p = .009) levels were significantly higher in the third trimester than the second trimester PE. In predicting PE, the area under the curve of cytokines and ICMs ranged from 0.51 for IL‐6 to 0.62 for TNF‐α.ConclusionPE may be characterized by a dominant Th1‐type immunity with higher levels of pro‐inflammatory cytokines and B7‐H1 proteins, but these variables may not be suitable for predicting PE.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Predicting Pe With Cytokines and B7 Moleculesmentioning

confidence: 99%

See 1 more Smart Citation

Immune checkpoint molecules B7‐1 and B7‐H1 as predictive markers of pre‐eclampsia: A case–control study in a Ghana

Akilla,

Nchor,

Banyeh

et al. 2024

Immunity Inflam & Disease

View full text Add to dashboard Cite

show abstract

“…Так, в исследованиях in vitro взаимодействие TIM-3-и PD-1 с соответствующими лигандами подавляет цитотоксическую активность CD8+Т-клеток, что может обеспечивать толерантность к фетальным антигенам [17,18]. Так было описано присутствие в децидуальной ткани беременных CD4+ и CD8+ Т-клеток с фенотипом эффекторных Т-клеток памяти, коэкспрессирующих PD-1 и Tim-3, и впервые идентифицировали их как Т-клетки в состоянии истощения [4]. Однако ранее Т-клетки c аналогичным фенотипом на начальных сроках беременности были описаны рядом авторов как Т-клетки с регуляторной (Th2) активностью [2].…”

Section: Discussionunclassified

“…Наиболее изученными ингибиторными рецепторами на Т-клетках являются молекулы CTLA-4 (cytotoxic T-lymphocyteantigen-4), РD-1 (programmed cell deathprotein-1) и TIM-3 (T cell immunoglobulin andmucin-domaincontaining-3). Запуск сигнальных путей при взаимодействии указанных рецепторов с соответствующими лигандами (CD80/86, PD-L1, Gal-9) приводит, с одной стороны, к подавлению функций эффекторных Т-клеток и смещению баланса в сторону Th2 ответа [2, 3], а с другой -к экспансии и усилению активности регуляторных T-клеток (Трег) [4]. Кроме того, повышенная экспрессия и коэкспрессия чек-поинт молекул характеризует дисфункциональное состояние (Т-клеточное «истощение»), отражающее прогрессирующее снижение функциональной активности Т-лимфоцитов при переходе эффекторных Т-клеток в клетки памяти [5,6].…”

Section: Introductionunclassified

Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy

et al. 2022

View full text Add to dashboard Cite

Background. Inhibitory receptors and their ligands (also called checkpoint molecules) are important feedback regulators of the immune response. However, their role in immunological adaptation during pregnancy remains poorly understood.The aim of the study was to evaluate the level of checkpoint molecule (PD-1, CTLA-4, Tim-3) expression in peripheral T cells in pregnant women compared with fertile non-pregnant women.Materials and methods. The study included 36 women in the second half of pregnancy without pregnancy complications, 12 of whom had extragenital pathology. The control group consisted of 28 age-matched fertile non-pregnant women. The proportion of CD8+PD-1+, CD8+TIM-3+, CD8+PD-1+TIM-3+, CD4+PD-1+, CD4+TIM-3+, and CD4+PD-1+TIM-3+ was evaluated by flow cytometry using the corresponding monoclonal antibodies (BD Biosciences, USA).Results. The proportion of CD4+Tim-3+ and CD8+PD-1+ Т cells and CD4+ and CD8+ Т lymphocytes co-expressing PD-1 and Tim-3 in the peripheral blood of pregnant women was statistically significantly higher than in non-pregnant women. An increase in CD4+Tim-3+ and CD8+PD-1+ T cells was observed both in pregnant women with and without extragenital pathology. However, pregnant women with extragenital pathology were characterized by a higher CD8+PD-1+ count and a smaller number of CD8+Tim-3+ cells, as well as by a lack of an increase in PD-1+Tim-3+ T cells typical of pregnant women. The number of comorbidities was directly correlated with the proportion of CD8+PD-1+ lymphocytes and inversely correlated with the proportion of CD8+Tim-3+ and CD4+ PD-1+Tim-3+ cells. In addition, the expression of checkpoint molecules was associated with gestational age (a direct correlation was found with the proportion of CD8+Tim-3+, CD4+PD-1+Tim-3+, and CD8+PD-1+Tim-3+ cells) and to a lesser extent – with the age of pregnant women (an inverse relationship was found with the proportion of CD8+Tim-3+ cells).Conclusion. Pregnant women in the second half of pregnancy are characterized by increased expression of PD-1 and Tim-3 molecules in peripheral T cells. At the same time, concomitant extragenital pathology affects the expression of these molecules.

show abstract

PD-L1 expression and characterization of its carrier macrophages in placentas with acute and specifically post-SARS-CoV-2 infection

Seefried,

Mittelberger,

Franitza

et al. 2024

Histochem Cell Biol

View full text Add to dashboard Cite

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, uncertainties about the virus and its dangers during pregnancy caused great uncertainty and fear, especially among pregnant women. New data suggest an increased risk of obstetric complications, including maternal complications, preterm labor, intrauterine growth restriction, hypertensive disorders, stillbirths, gestational diabetes and risk, of neonatal developmental disorders. In addition, preeclampsia (PE)-like syndromes were also induced by severe COVID-19 infection. Therefore, the aim of this study was to investigate the expression of CD68 and CD163 and PD-L1 on placental tissues from acute covid patients, patients who survived a covid-19 infection and normal term controls that are known to be dysregulated in preeclampsia cases. We examined a total of 60 placentas from women that had given birth to female or male offspring in the University Hospital Augsburg. We investigated ten acute COVID-19 females, ten acute COVID-19 males, ten post-COVID-19 females, ten post-COVID-19 males, ten female term controls, and ten male term controls. Immunohistochemical staining against CD68, CD163, and PD-L1 was performed and the expression of the markers was evaluated with an immunoreactive score (percentage score). Identity of CD163- or PD-L1 expressing cells was analyzed by double immune fluorescence analyses. In opposite to PE, CD163 positive maternal macrophages are significantly upregulated in the decidua of male acute COVID-19 placentas. PD-L1 is significantly upregulated on male acute- and post-COVID-19 decidual immune cells and on male post-COVID-19 extravillous trophoblast cells. Surprisingly the observed effects are related to the fetal gender as they were not observed in female offsprings. Further investigation is necessary to analyze especially the imprinting effect of this infection.

show abstract

The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia—A Narrative Review

Cited by 16 publications

References 55 publications

Immune checkpoint molecules B7‐1 and B7‐H1 as predictive markers of pre‐eclampsia: A case–control study in a Ghana

Immune checkpoint molecules B7‐1 and B7‐H1 as predictive markers of pre‐eclampsia: A case–control study in a Ghana

Expression of inhibitory receptors PD-1, CTLA-4, and Tim-3 by peripheral T cells during pregnancy

PD-L1 expression and characterization of its carrier macrophages in placentas with acute and specifically post-SARS-CoV-2 infection

Contact Info

Product

Resources

About