@article{MTMT:30914524, title = {Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild-type and pituitary adenylate cyclase-activating polypeptide-deficient mice}, url = {https://m2.mtmt.hu/api/publication/30914524}, author = {Meggyes, Mátyás and Lajkó, Adrienn and Fülöp, Balázs Dániel and Reglődi, Dóra and Szereday, László}, doi = {10.1111/aji.13212}, journal-iso = {AM J REPROD IMMUNOL}, journal = {AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY}, volume = {83}, unique-id = {30914524}, issn = {1046-7408}, abstract = {PACAP is a neuropeptide having several regulatory functions in the nervous system and in peripheral organs including those of the reproductive system. PACAP-deficient male mice have several morphological, biochemical, behavioral defects and show disturbed signaling in spermatogenesis affecting fertility in PACAP KO mice. Reproductive functions such as fertility, mating and maternal behaviors have been widely investigated, but no immune analyses are available regarding the testicular immune-privileged environment in male PACAP-deficient mice.Therefore, we performed detailed immunophenotyping of testicular immune cells and investigated the expression of TIM-3 and PD-1 immune-checkpoint molecules of immune cells together with the detection of Galectin-9 and perforin. We investigated the percentage of numerous immune cell populations in the testis of wild-type and PACAP-deficient mice.We demonstrated a significant increase in the frequency of testicular CD8+ T cells together with the decrease of Treg cell number obtained from PACAP KO mice compared to wild-type mice. Investigating immune-checkpoint receptors, only PD-1 showed a significantly decreased expression in CD8+ T cells in PACAP KO mice compared to wild-type suggesting an impaired PD-1/PD-L1 pathway. Regarding TIM-3 expression, we did not find any significant difference between the investigated groups.We hypothesize that these local changes may result in an immune activation with disturbed testicular immunoregulation in PACAP KO mice, however, determining the exact function requires further investigations. Our data further support the view that besides a systemic immune tolerance, localized active immunosuppression is involved in the regulation of testicular immune privilege.}, keywords = {NEUROPEPTIDE; PACAP; PD-1; PD-L1; Galectin-9; TIM-3}, year = {2020}, eissn = {1600-0897}, orcid-numbers = {Szereday, László/0000-0002-1208-2969} } @article{MTMT:30418875, title = {Involvement of the PD-1/PD-L1 Co-Inhibitory Pathway in the Pathogenesis of the Inflammatory Stage of Early-Onset Preeclampsia.}, url = {https://m2.mtmt.hu/api/publication/30418875}, author = {Meggyes, Mátyás and Mikó, Éva and Lajkó, Adrienn and Csiszár, Beáta and Sándor, Barbara and Mátrai, Péter and Tamás, Péter and Szereday, László}, doi = {10.3390/ijms20030583}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {20}, unique-id = {30418875}, issn = {1661-6596}, abstract = {The programmed cell death protein 1 (PD-1) receptor has been reported to downregulate T cell activation effectively via binding to its ligands PD-L1 or PD-L2 in a negative co-stimulatory manner. Little is known about the involvement of PD-1 mediated immunoregulation in pregnancy and in pregnancy-related disorders. In this work, we investigated the possible role of the PD-1 co-stimulatory pathway in the pathogenesis of the clinical phase of early-onset preeclampsia characterized by a systemic maternal inflammatory response. We performed a cross-sectional study for comparative analysis of phenotypic and functional characteristics of peripheral blood mononuclear cells in women with early-onset preeclampsia and third-trimester healthy pregnant controls. According to our findings, enhanced expression of either PD-1 or its ligand PD-L1, or both, on the cell surface of effector cells (T cells, natural killer (NK) cells, natural killer T (NKT)-like cells) and Tregs could be observed, but PD-1 expression did not correlate with effector cells exhaustion. These results suggest the failure of the axis to downregulate Th1 responses, contributing thereby to the exaggerated immunoactivation observed in early-onset preeclampsia.}, keywords = {Inflammation; PREECLAMPSIA; EARLY-ONSET; PD-1; PD-L1; Immune checkpoint}, year = {2019}, eissn = {1422-0067}, orcid-numbers = {Sándor, Barbara/0000-0002-7028-4227; Szereday, László/0000-0002-1208-2969} } @article{MTMT:3398343, title = {Comparative analysis of decidual and peripheral immune cells and immune-checkpoint molecules during pregnancy in wild-type and PACAP-deficient mice}, url = {https://m2.mtmt.hu/api/publication/3398343}, author = {Lajkó, Adrienn and Meggyes, Mátyás and Fülöp, Balázs Dániel and Gede, Noémi and Reglődi, Dóra and Szereday, László}, doi = {10.1111/aji.13035}, journal-iso = {AM J REPROD IMMUNOL}, journal = {AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY}, volume = {80}, unique-id = {3398343}, issn = {1046-7408}, abstract = {ProblemPACAP is a neuropeptide having a major relevance in the nervous system and in several peripheral organs including those of the reproductive system. PACAP-deficient mice have several morphological, biochemical, behavioral defects, and show reduced fertility. Female reproductive functions such as fertility, mating behavior, maternal behaviors, and implantation alterations have been widely investigated, but no comparative immune analyses are available in pregnant wild-type (WT) and PACAP knockout (KO) mice. Methods of studyTherefore, we performed a detailed immunophenotyping of decidual and peripheral immune cells and investigated the expression of two immune-checkpoint molecules by immune cells together with immunohistochemistry detecting Galectin-9 in placental tissues. We investigated the percentage of numerous immune cell populations in the periphery and in the decidua of pregnant mice. ResultsWe demonstrated a significant increase in the frequency of decidual Gal-9+ Th cells obtained from PACAP KO mice compared to the decidua of WT mice. We could not determine statistical differences in TIM-3 and programmed cell death-1 expression by different immune cells in the decidua and in the periphery between WT and KO mice. In conclusion, we could not find any significant alteration either in the distribution or in the cytotoxicity of the investigated decidual immune cells which could elucidate any reproductive alterations in PACAP KO mice. ConclusionThe only remarkable finding is the recruitment of Gal-9+ Th cells to the decidua promoting local immune homeostasis in PACAP KO mice, which nevertheless cannot explain the reduced fertility observed in these mice.}, keywords = {RECEPTOR; NEUROPEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; SIGNALING PATHWAYS; TOLERANCE; immunology; pregnancy; PROGESTERONE; fertility; Autoimmune; INTESTINAL POLYPEPTIDE; PD-1; PD-1; Galectin-9; TIM-3}, year = {2018}, eissn = {1600-0897}, orcid-numbers = {Szereday, László/0000-0002-1208-2969} } @article{MTMT:3352310, title = {The immunological effect of Galectin-9/TIM-3 pathway after low dose Mifepristone treatment in mice at 14.5 day of pregnancy}, url = {https://m2.mtmt.hu/api/publication/3352310}, author = {Lajkó, Adrienn and Meggyes, Mátyás and Polgár, Beáta and Szereday, László}, doi = {10.1371/journal.pone.0194870}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {13}, unique-id = {3352310}, issn = {1932-6203}, abstract = {The abortifacient Mifepristone (RU486) has proven to be a safe, effective, acceptable option for millions of women seeking abortion during the first and second trimester of pregnancy although its precise mechanism of action is not well understood. The main objective of this study was to investigate the impact of low dose Mifepristone administration on placental Galectin-9 (Gal-9) expression, as well as its effect on the cell surface expression of Gal-9, TIM-3 and CD107a molecules by different T and NK cell subsets. A model of Mifepristone-induced immunological changes was established in syngeneic pregnant BALB/c mice. RU486-induced alteration in placental Gal-9 expression was determined by immunohistochemistry. For immunophenotypic analysis, mid-pregnancy decidual lymphocytes and peripheral mononuclear cells were obtained from Mifepristone treated and control mice at the 14.5 day of gestation. TIM-3 and Gal-9 expression by peripheral and decidual immune cells were examined by flow cytometry. Our results revealed a dramatically decreased intracellular Gal-9 expression in the spongiotrophoblast layer of the haemochorial placenta in Mifepristone treated pregnant mice. Although low dose RU486 treatment did not cause considerable change in the phenotypic distribution of decidual and peripheral immune cells, it altered the Gal-9 and TIM-3 expression by different NK and T cell subsets. In addition, the treatment significantly decreased the CD107a expression by decidual TIM-3+ NK cells, but increased its expression by decidual NKT cell compared to the peripheral counterparts. These findings suggest that low dose Mifepristone administration might induce immune alterations in both progesterone dependent and independent way.}, year = {2018}, eissn = {1932-6203}, orcid-numbers = {Szereday, László/0000-0002-1208-2969} } @article{MTMT:3307938, title = {The possible role of CD8+/Valpha7.2+/CD161++ T (MAIT) and CD8+/Valpha7.2+/CD161(lo) T (MAIT-like) cells in the pathogenesis of early-onset pre-eclampsia.}, url = {https://m2.mtmt.hu/api/publication/3307938}, author = {Meggyes, Mátyás and Szanto, J and Lajkó, Adrienn and Farkas, Bálint and Várnagy, Ákos and Tamás, Péter and Hantosi, Eszter and Mikó, Éva and Szereday, László}, doi = {10.1111/aji.12805}, journal-iso = {AM J REPROD IMMUNOL}, journal = {AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY}, volume = {79}, unique-id = {3307938}, issn = {1046-7408}, abstract = {PROBLEM: The objective of this study was to compare the expressions of different immune-checkpoint molecules by MAIT and MAIT-like cells in healthy pregnancy and in early-onset pre-eclampsia. METHOD OF STUDY: Peripheral blood mononuclear cells (PBMC) were stained with monoclonal antibodies to characterize MAIT and MAIT-like cells. Flow cytometric analyses were used to measure PD-1, TIM-3, activation markers, and intracellular perforin expression. RESULTS: We identified CD3+/CD8+/Valpha7.2+/CD161++ MAIT cells and a minor cell population characterized by CD3+/CD8+/Valpha7.2+/CD161(lo) surface markers. In measuring the expression of PD-1 receptor, we found a significantly lower expression by MAIT cells in women with early-onset pre-eclampsia. CD69 expression by MAIT cells was significantly elevated in early-onset pre-eclamptic patients. Intracellular perforin content by MAIT and PD-1+ MAIT cells was significantly increased in pre-eclamptic patients compared with healthy individuals. CONCLUSION: Altered frequency and reduced PD-1 expression combined together with the elevated perforin content of MAIT cells insinuate their potential roles in the pathogenesis of early-onset pre-eclampsia.}, year = {2018}, eissn = {1600-0897}, orcid-numbers = {Farkas, Bálint/0000-0003-0638-2057; Szereday, László/0000-0002-1208-2969} } @book{MTMT:3072069, title = {5th Interdisciplinary Doctoral Conference : Book of abstracts =V. Interdiszciplináris Doktorandusz Konferencia : Absztraktkötet}, url = {https://m2.mtmt.hu/api/publication/3072069}, isbn = {9789634290377}, editor = {Ács, Kamilla and Bencze, Noémi and Bódog, Ferenc and Haffner, Tamás and Hegyi, Dávid and Horváth, Orsolya Melinda and Hüber, Gabriella Margit and Kovács, Áron and Kis Kelemen, Bence and Lajkó, Adrienn and Schilli, Gabriella Krisztina and Stankovicsné Szendi, Anna and Szilágyi, Tamás Gábor and Varga, Zoltán}, publisher = {Doctoral Student Association of the University of Pécs}, unique-id = {3072069}, year = {2016}, orcid-numbers = {Varga, Zoltán/0000-0002-2494-6664} } @article{MTMT:3071246, title = {Feto-maternal immune regulation by programmed cell death protein-1 (PD-1) molecule in pregnant mice}, url = {https://m2.mtmt.hu/api/publication/3071246}, author = {Lajkó, Adrienn and Meggyes, Mátyás and Szanto, J and Mikó, Éva and Szereday, László}, doi = {10.1016/j.jri.2016.04.147}, journal-iso = {J REPROD IMMUNOL}, journal = {JOURNAL OF REPRODUCTIVE IMMUNOLOGY}, volume = {115}, unique-id = {3071246}, issn = {0165-0378}, year = {2016}, eissn = {1872-7603}, pages = {48}, orcid-numbers = {Szereday, László/0000-0002-1208-2969} } @article{MTMT:2931283, title = {Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy.}, url = {https://m2.mtmt.hu/api/publication/2931283}, author = {Meggyes, Mátyás and Lajkó, Adrienn and Palkovics, Tamás and Totsimon, A and Illés, Zsolt László and Szereday, László and Mikó, Éva}, doi = {10.1016/j.placenta.2015.07.124}, journal-iso = {PLACENTA}, journal = {PLACENTA}, volume = {36}, unique-id = {2931283}, issn = {0143-4004}, abstract = {INTRODUCTION: Immunoregulation implies the activation of negative pathways leading to the modulation of specific immune responses. Co-inhibitory receptors (such as PD-1 and TIM-3) represent possible tools for this purpose. PD-1 and TIM-3 have been demonstrated to be present on immune cells suggesting general involvement in immunosuppression such as fetomaternal tolerance. The aim of our study was to investigate the expression pattern of PD-1, TIM-3, and its ligand Gal-9 on different immune cell subsets in the peripheral blood and at the fetomaternal interface in pregnant mice. METHODS: TIM-3 and PD-1 expression by peripheral and decidual immune cells from pregnant BALB-c mice in 2 weeks of gestational age were measures by flow cytometry. Placental galectin-9 expression was determined by immunohistochemically and RT-PCR. RESULTS: Gal-9 was found to be present in the spongiotrophoblast layer of the haemochorial placenta. Decidual NK, NKT and gamma/delta T cells showed increased PD-1 expression and reduced cytotoxic potential when compared to the periphery. TIM-3 expression by NK cells and gamma/delta T cells is similar both in the periphery and in the decidua, notably, their relative TIM-3 expression is increased locally which is associated with reduced lytic activity. Decidual NKT cells exhibit a reduced TIM-3 expression with increased relative receptor expression and a slightly increased cytotoxicity when compared to the periphery. DISCUSSION: Our data reveals a particularly complex, tissue and cell type specific immunoregulatory mechanism by the investigated co-inhibitory receptors at the fetomaternal interface.}, year = {2015}, eissn = {1532-3102}, pages = {1153-1160}, orcid-numbers = {Illés, Zsolt László/0000-0001-9655-0450; Szereday, László/0000-0002-1208-2969} }