TY - JOUR AU - Meggyes, Mátyás AU - Lajkó, Adrienn AU - Fülöp, Balázs Dániel AU - Reglődi, Dóra AU - Szereday, László TI - Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild-type and pituitary adenylate cyclase-activating polypeptide-deficient mice JF - AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY J2 - AM J REPROD IMMUNOL VL - 83 PY - 2020 IS - 3 PG - 10 SN - 1046-7408 DO - 10.1111/aji.13212 UR - https://m2.mtmt.hu/api/publication/30914524 ID - 30914524 N1 - Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary Janos Szentagothai Research Center, Pecs, Hungary Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, Medical School, University of Pecs, Pecs, Hungary Cited By :5 Export Date: 2 October 2023 CODEN: AAJID Correspondence Address: Szereday, L.; Department of Medical Microbiology and Immunology, Hungary; email: szereday.laszlo@pte.hu AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Meggyes, Mátyás AU - Mikó, Éva AU - Lajkó, Adrienn AU - Csiszár, Beáta AU - Sándor, Barbara AU - Mátrai, Péter AU - Tamás, Péter AU - Szereday, László TI - Involvement of the PD-1/PD-L1 Co-Inhibitory Pathway in the Pathogenesis of the Inflammatory Stage of Early-Onset Preeclampsia. JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 20 ET - 0 PY - 2019 IS - 3 PG - 11 SN - 1661-6596 DO - 10.3390/ijms20030583 UR - https://m2.mtmt.hu/api/publication/30418875 ID - 30418875 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Lajkó, Adrienn AU - Meggyes, Mátyás AU - Fülöp, Balázs Dániel AU - Gede, Noémi AU - Reglődi, Dóra AU - Szereday, László TI - Comparative analysis of decidual and peripheral immune cells and immune-checkpoint molecules during pregnancy in wild-type and PACAP-deficient mice JF - AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY J2 - AM J REPROD IMMUNOL VL - 80 ET - 0 PY - 2018 IS - 4 PG - 11 SN - 1046-7408 DO - 10.1111/aji.13035 UR - https://m2.mtmt.hu/api/publication/3398343 ID - 3398343 N1 - Funding Agency and Grant Number: EFOP [3.6.2-16-2017-00008]; Neuroscience Centre of Pecs; National Research, Development and Innovation Office [K115874, K119529, K119759]; National Excellence Program [2017-1.2.1-NKP-2017-00002]; PTE AOK KA Research Grant [KA-2018-07]; PEPSYS [GINOP-2.3.2-15-2016-00050]; MTA-TKI [14016]; Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary [20765-3/2018/FEKUTSTRAT] Funding text: EFOP, Grant/Award Number: 3.6.2-16-2017-00008; Neuroscience Centre of Pecs; National Research, Development and Innovation Office, Grant/Award Number: K115874, K119529 and K119759; National Excellence Program, Grant/Award Number: 2017-1.2.1-NKP-2017-00002; PTE AOK KA Research Grant, Grant/Award Number: KA-2018-07; PEPSYS, Grant/Award Number: GINOP-2.3.2-15-2016-00050; MTA-TKI, Grant/Award Number: 14016; Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, Grant/Award Number: 20765-3/2018/FEKUTSTRAT AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Lajkó, Adrienn AU - Meggyes, Mátyás AU - Polgár, Beáta AU - Szereday, László TI - The immunological effect of Galectin-9/TIM-3 pathway after low dose Mifepristone treatment in mice at 14.5 day of pregnancy JF - PLOS ONE J2 - PLOS ONE VL - 13 PY - 2018 IS - 3 PG - 16 SN - 1932-6203 DO - 10.1371/journal.pone.0194870 UR - https://m2.mtmt.hu/api/publication/3352310 ID - 3352310 N1 - Funding Agency and Grant Number: Hungarian National Research Fund [OTKA K104960, K119529]; TAMOP [4.2.4. A/2-11-1-2012-0001]; Hungarian Academy of Sciences Funding text: This work was supported by grants from Hungarian National Research Fund (OTKA K104960 and K119529), TAMOP 4.2.4. A/2-11-1-2012-0001 and the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences to L. Szereday.; This work was supported by grants from Hungarian National Research Fund (OTKA K104960 and K119529), TAMOP 4.2.4. A/2-11-1-2012-0001 and the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences to L. Szereday. The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pecs, Hungary. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Meggyes, Mátyás AU - Szanto, J AU - Lajkó, Adrienn AU - Farkas, Bálint AU - Várnagy, Ákos AU - Tamás, Péter AU - Hantosi, Eszter AU - Mikó, Éva AU - Szereday, László TI - 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. JF - AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY J2 - AM J REPROD IMMUNOL VL - 79 PY - 2018 IS - 2 PG - 10 SN - 1046-7408 DO - 10.1111/aji.12805 UR - https://m2.mtmt.hu/api/publication/3307938 ID - 3307938 AB - 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. LA - English DB - MTMT ER - TY - BOOK ED - Ács, Kamilla ED - Bencze, Noémi ED - Bódog, Ferenc ED - Haffner, Tamás ED - Hegyi, Dávid ED - Horváth, Orsolya Melinda ED - Hüber, Gabriella Margit ED - Kovács, Áron ED - Kis Kelemen, Bence ED - Lajkó, Adrienn ED - Schilli, Gabriella Krisztina ED - Stankovicsné Szendi, Anna ED - Szilágyi, Tamás Gábor ED - Varga, Zoltán TI - 5th Interdisciplinary Doctoral Conference : Book of abstracts =V. Interdiszciplináris Doktorandusz Konferencia : Absztraktkötet ET - 0 PB - Pécsi Tudományegyetem Doktorandusz Önkormányzat CY - Pécs PY - 2016 SP - 206 SN - 9789634290377 UR - https://m2.mtmt.hu/api/publication/3072069 ID - 3072069 LA - English DB - MTMT ER - TY - JOUR AU - Lajkó, Adrienn AU - Meggyes, Mátyás AU - Szanto, J AU - Mikó, Éva AU - Szereday, László TI - Feto-maternal immune regulation by programmed cell death protein-1 (PD-1) molecule in pregnant mice JF - JOURNAL OF REPRODUCTIVE IMMUNOLOGY J2 - J REPROD IMMUNOL VL - 115 PY - 2016 SP - 48 SN - 0165-0378 DO - 10.1016/j.jri.2016.04.147 UR - https://m2.mtmt.hu/api/publication/3071246 ID - 3071246 LA - English DB - MTMT ER - TY - JOUR AU - Meggyes, Mátyás AU - Lajkó, Adrienn AU - Palkovics, Tamás AU - Totsimon, A AU - Illés, Zsolt László AU - Szereday, László AU - Mikó, Éva TI - Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy. JF - PLACENTA J2 - PLACENTA VL - 36 PY - 2015 IS - 10 SP - 1153 EP - 1160 PG - 8 SN - 0143-4004 DO - 10.1016/j.placenta.2015.07.124 UR - https://m2.mtmt.hu/api/publication/2931283 ID - 2931283 AB - 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. LA - English DB - MTMT ER -