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1.
Clin Immunol ; 224: 108663, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33401032

RESUMO

Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with a high incidence among women of childbearing age. Recent studies have reported that women with AIT are more susceptible to infertility, miscarriage and preterm birth. It has been investigated that abnormal changes in maternal immune system and maternal-fetal interface can dampen the immune tolerance between mother and fetus, which underlie the pathogenesis of adverse pregnancy outcomes. Hence, we summarize the immunological changes related to adverse reproductive outcomes in AIT and highlight the respective contributions of both humoral and cellular immune dysfunctions to pregnancy failures. Moreover, the direct impacts of AIT on maternal-fetal immune activation and biological influences to trophoblasts are discussed as well. All these associations require confirmation in larger studies, and the pathogenic mechanisms need to be better understood, which might provide useful information for clinical diagnosis and therapy of AIT.

2.
Am J Reprod Immunol ; 84(5): e13304, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32662111

RESUMO

Caused by a novel type of virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) constitutes a global public health emergency. Pregnant women are considered to have a higher risk of severe morbidity and even mortality due to their susceptibility to respiratory pathogens and their particular immunologic state. Several studies assessing SARS-CoV-2 infection during pregnancy reported adverse pregnancy outcomes in patients with severe conditions, including spontaneous abortion, preterm labor, fetal distress, cesarean section, preterm birth, neonatal asphyxia, neonatal pneumonia, stillbirth, and neonatal death. However, whether these complications are causally related to SARS-CoV-2 infection is not clear. Here, we reviewed the scientific evidence supporting the contributing role of Treg/Th17 cell imbalance in the uncontrolled systemic inflammation characterizing severe cases of COVID-19. Based on the recognized harmful effects of these CD4+ T-cell subset imbalances in pregnancy, we speculated that SARS-CoV-2 infection might lead to adverse pregnancy outcomes through the deregulation of otherwise tightly regulated Treg/Th17 ratios, and to subsequent uncontrolled systemic inflammation. Moreover, we discuss the possibility of vertical transmission of COVID-19 from infected mothers to their infants, which could also explain adverse perinatal outcomes. Rigorous monitoring of pregnancies and appropriate measures should be taken to prevent and treat early eventual maternal and perinatal complications.

3.
J Leukoc Biol ; 108(3): 983-998, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32386458

RESUMO

Decidual macrophages are in close contact with trophoblast cells during placenta development, and an appropriate crosstalk between these cellular compartments is crucial for the establishment and maintenance of a healthy pregnancy. During different phases of gestation, macrophages undergo dynamic changes to adjust to the different stages of fetal development. Trophoblast-secreted factors are considered the main modulators responsible for macrophage differentiation and function. However, the phenotype of these macrophages induced by trophoblast-secreted factors and the factors responsible for their polarization has not been elucidated. In this study, we characterized the phenotype and function of human trophoblast-induced macrophages. Using in vitro models, we found that human trophoblast-educated macrophages were CD14+ CD206+ CD86- and presented an unusual transcriptional profile in response to TLR4/LPS activation characterized by the expression of type I IFN-ß expression. IFN-ß further enhances the constitutive production of soluble programmed cell death ligand 1 (PD-L1) from trophoblast cells. PD-1 blockage inhibited trophoblast-induced macrophage differentiation. Soluble PD-L1 (sPD-L1) was detected in the blood of pregnant women and increased throughout the gestation. Collectively, our data suggest the existence of a regulatory circuit at the maternal fetal interface wherein IFN-ß promotes sPD-L1 expression/secretion by trophoblast cells, which can then initiate a PD-L1/PD-1-mediated macrophage polarization toward an M2 phenotype, consequently decreasing inflammation. Macrophages then maintain the expression of sPD-L1 by the trophoblasts through IFN-ß production induced through TLR4 ligation.

4.
J Reprod Immunol ; 139: 103122, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32244166

RESUMO

The 2019 novel coronavirus disease (COVID-19) was first detected in December 2019 and became epidemic in Wuhan, Hubei Province, China. COVID-19 has been rapidly spreading out in China and all over the world. The virus causing COVID-19, SARS-CoV-2 has been known to be genetically similar to severe acute respiratory syndrome coronavirus (SARS-CoV) but distinct from it. Clinical manifestation of COVID-19 can be characterized by mild upper respiratory tract infection, lower respiratory tract infection involving non-life threatening pneumonia, and life-threatening pneumonia with acute respiratory distress syndrome. It affects all age groups, including newborns, to the elders. Particularly, pregnant women may be more susceptible to COVID-19 since pregnant women, in general, are vulnerable to respiratory infection. In pregnant women with COVID-19, there is no evidence for vertical transmission of the virus, but an increased prevalence of preterm deliveries has been noticed. The COVID-19 may alter immune responses at the maternal-fetal interface, and affect the well-being of mothers and infants. In this review, we focused on the reason why pregnant women are more susceptible to COVID-19 and the potential maternal and fetal complications from an immunological viewpoint.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Complicações Infecciosas na Gravidez/imunologia , China , Infecções por Coronavirus/patologia , Feminino , Humanos , Pandemias , Pneumonia Viral/patologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Nascimento Prematuro/etiologia
5.
Front Immunol ; 11: 279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32180770

RESUMO

Aerobic glycolysis is a recognized feature shared by tumors, leading to the accumulation of lactic acid in their local microenvironments. Like the tumors, the blastocysts, placenta, trophoblasts and decidual immune cells can also produce a large amount of lactic acid through aerobic glycolysis during the early pregnancy. Moreover, the placenta expresses the transporters of the lactic acid. While several studies have described the role of lactic acid in the tumor microenvironment, especially lactic acid's modulation of immune cells, the role of lactic acid produced during pregnancy is still unclear. In this paper, we reviewed the scientific evidence detailing the effects of lactic acid in the tumor microenvironment. Based on the influence of the lactic acid on immune cells and tumors, we proposed that lactic acid released in the unique uterine environment could have similar effects on the trophoblast cells and immune cells during the early pregnancy.

6.
Am J Reprod Immunol ; 82(4): e13168, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299118

RESUMO

PROBLEM: Studies assessing the association between vitamin D deficiency and preeclampsia (PE) have not reached a consensus. The study aimed to investigate the role of vitamin D in the occurrence of PE through its immune-modulatory effects on Treg/Th17 cell ratio. METHOD OF STUDY: This is a case-control study of third-trimester pregnant women. Peripheral blood 25(OH)D, TGF-ß1, IL-6, and Treg/Th17 cells were analyzed. RESULTS: One hundred and sixty-three pregnant women were recruited, and 100 women (59 with a normal pregnancy (NP) and 41 with PE) were included in the study. The prevalence of vitamin D deficiency was 69.3%. Vitamin D-deficient pregnant women (25(OH) D < 20 ng/mL) had fivefold higher risk to develop PE than those with 25(OH)D level ≥20 ng/mL (OR = 5.29, CI 95% = 1.81-15.41). PE patients had lower circulating levels of 25(OH)D (12.83 ± 5.37 ng/mL vs 20.76 ± 9.63 ng/mL, P < .0001) and Treg/Th17 cell ratio (1.61 ± 0.71% vs 2.94 ± 1.35%, P < .0001), compared to women with NP. In patients with PE, 25(OH)D level correlated negatively with IL-6 levels (r = -.60, P < .0001) and positively with Treg/Th17 cell ratio (r = .89, P < .0001). We also observed a negative relationship between IL-6 levels and Treg/Th17 cell ratio (r = -.54, P = .0002). CONCLUSION: Our study demonstrated the correlation between low plasma vitamin D level and altered immune parameters in PE. We propose that, through its effects on Treg/Th17 cell ratio, vitamin D might influence the occurrence of PE.


Assuntos
Pré-Eclâmpsia/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Deficiência de Vitamina D/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/epidemiologia , Gravidez , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitaminas/sangue , Adulto Jovem
7.
Am J Reprod Immunol ; 81(3): e13076, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30582662

RESUMO

PROBLEM: Embryo implantation depends on the interactions between the developing embryo and the maternal endometrium. Signals originating from the decidua play a critical role in the process of implantation and trophoblast invasion; however, the molecular mechanisms mediating this interaction are poorly understood. The objective of this study was to develop in vitro models that would mimic the processes of attachment, migration, and early invasion of the trophoblast. METHODS OF STUDY: First trimester trophoblast cells (Sw.71 cells) were cultured in low attachment plates to form blastocyst-like spheroids (BLS). Epithelial-mesenchymal transition (EMT) characterization during BLS formation was determined by RT-PCR and Western Blot. The two 3D in vitro culture models consist of (a) trophoblast migration: BLS cultured in suspension (b) trophoblast invasion: human endometrium stromal cells (HESC) plated in the bottom of a 96-well plate, covered by Matrigel and BLS transferred on top. Matrigel was used to mimic the human endometrial extracellular matrix. RESULTS: Using 3D cell culture systems and real-time imaging, we are able to determine the impact of endometrial factors on trophoblast cell function. Endometrial stromal cells promote blastocyst-like spheroid migration of trophoblast cells and invasion of the extracellular matrix. CONCLUSION: We report the characterization of 3D in vitro models to evaluate the interaction between endometrial cells and trophoblast during the process of migration and invasion. The models are useful tools in order to further study the molecular mechanism of embryo-maternal uterine cells interactions.


Assuntos
Blastocisto/citologia , Endométrio/fisiologia , Troca Materno-Fetal/fisiologia , Gravidez , Esferoides Celulares/fisiologia , Células Estromais/fisiologia , Trofoblastos/fisiologia , Comunicação Celular , Técnicas de Cultura de Células , Movimento Celular , Células Cultivadas , Implantação do Embrião , Desenvolvimento Embrionário , Feminino , Humanos
8.
Am J Reprod Immunol ; 81(2): e13079, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30578744

RESUMO

PROBLEM: This study aims to determine the expression and localization of programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) in the testes of mice at different developmental stages. METHOD OF STUDY: By means of RT-qPCR, Western blot and immunofluorescence, the expression and localization of PD-1 and PD-L1 were detected in the testicular tissues of mice at different postnatal times: P7, P14, P21, P28, P35, and adulthood. Meanwhile, the level of soluble PD-L1 (sPD-L1) was evaluated by ELISA in the testicular interstitial fluid (IF) of the adult mice, culture supernatants of TM4 cell lines (Sertoli cells lines), and primary Sertoli cells at P14. RESULTS: Pd-1 mRNA levels were unexpectedly low. From P7 to P21, there was limited PD-1 protein detected while PD-1 was evident at P28 and afterward at significantly higher levels than at P14 and P21 (P < 0.05). Despite being found in the interstitial area at P7, P14, and P21, PD-1 was also detected in the germ cells of the seminiferous tubules after P28. Pd-l1 mRNA exhibited age-related changes, peaking at P21, while PD-L1 protein was constitutively expressed at any stage, specifically localized in the nucleus of Sertoli cells. Moreover, the level of sPD-L1 in IF was significantly higher than that in the culture supernatants of both TM4 and primary Sertoli cells at P14. CONCLUSIONS: PD-1 and PD-L1 were present in the testicular tissue of adult mice. The expression and localization of PD-1 fluctuated with age, and PD-1 was mainly localized to advanced germ cells, suggesting that it may play a role in spermiogenesis. PD-L1 was constitutively expressed in the nucleus of Sertoli cells, which could secrete sPD-L1 into the testicular interstitial space and thus may be involved in testicular immune privilege.


Assuntos
Antígeno B7-H1/genética , Receptor de Morte Celular Programada 1/genética , RNA Mensageiro/genética , Células de Sertoli/fisiologia , Testículo/fisiologia , Animais , Apoptose , Antígeno B7-H1/metabolismo , Linhagem Celular , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Privilégio Imunológico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Receptor de Morte Celular Programada 1/metabolismo , Espermatogênese/genética , Testículo/patologia
9.
Am J Reprod Immunol ; 80(4): e13018, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29984444

RESUMO

Recurrent spontaneous abortion (RSA) is a growing problem worldwide. In a majority of cases, the cause remains unknown but there is increasing evidence that immunologic factors play an important role. Intravenous immunoglobulin (IVIg) therapy has been proposed to have immune modulatory effects and therefore been applicable for the treatment of patients with RSA. Although its efficacy is still controversial, several recent studies suggest that IVIg treatment may improve pregnancy outcomes. CD4+ T cells and their related cytokines play an important role in maternal-fetal immune regulation, and an imbalance of Th17/Treg cell ratio has been proposed as a cause for RSA. We review the scientific evidence supporting a modulatory effect of IVIg on Th17/Treg cell balance and discuss the potential mechanisms how IVIg might enhance Treg cells function. We propose that correction of Th17/Treg cell dysregulation could be one of the mechanisms that can explain the positive therapeutic effects of IVIg therapy. Consequently, selecting patients with abnormal Th17/Treg cell ratios could increase the success of IVIg therapy.


Assuntos
Aborto Habitual/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Aborto Habitual/imunologia , Imunidade Adaptativa/imunologia , Contagem de Linfócito CD4 , Feminino , Humanos , Gravidez , Resultado da Gravidez
10.
Front Immunol ; 9: 3142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30687334

RESUMO

Dysfunction of decidual macrophages (DMs) is considered a critical event in the pathogenesis of pre-eclampsia (PE). T cell immunoglobulin mucin 3 (Tim-3) is an important negative regulatory molecule that induces immune tolerance by interacting with its ligand Galectin-9 (Gal-9) and thus modulating function of various immune cells, including macrophages. However, the regulatory effects of Tim-3/Gal-9 signaling on DMs polarization and its role in PE remain unclear. In this study, we established a PE-like rat model by administering 1.0 µg/kg lipopolysaccharide (LPS) to normal pregnant Sprague-Dawley rats via the tail vein at embryonic day 5 (E5). Apart from the pre-eclamptic manifestations, increased M1 subtype and decreased M2 subtype were observed at the maternal-fetal interface, as well as increased pro-inflammatory cytokines (TNF-α and IL-1ß) and reduced anti-inflammatory cytokines (TGF-ß and IL-10). Moreover, the expression of Tim-3 in DMs and that of Gal-9 at the maternal-fetal interface were reduced. After administration of recombinant Galectin-9 (rGal-9) protein, we found that liver and renal injuries and maternofetal placental functional deficiency, including inadequate trophoblast cells invasion, impaired spiral artery remodeling and fetal capillary development, were reversed. In addition, the polarization of DMs was inclined to M2 subtype, which was similar to the polarization of DMs in the control rats but contrary to the PE-like rats. Interestingly, at E9, the expression of Tim-3 in DMs and that of Gal-9 at the maternal-fetal interface were significantly increased in the rGal-9 protein intervention group. Taken together, our findings show that administration of rGal-9 protein can alleviate the PE-like rat manifestations induced by LPS. This finding may be related to the activation of the Tim-3/Gal-9 signaling pathway, which promotes DMs polarization dominantly shifting to M2 subtype. Moreover, upregulation of Tim-3 in DMs and Gal-9 at the maternal-fetal interface at E9 suggests that Tim-3/Gal-9 pathway may play some important roles in early pregnancy and even embryo development.


Assuntos
Decídua/imunologia , Decídua/metabolismo , Galectinas/metabolismo , Lipopolissacarídeos/efeitos adversos , Macrófagos/imunologia , Macrófagos/metabolismo , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/metabolismo , Animais , Pressão Sanguínea , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Imunofluorescência , Galectinas/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Hipertensão , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Rim/imunologia , Rim/metabolismo , Rim/patologia , Lipopolissacarídeos/imunologia , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Ativação de Macrófagos/imunologia , Troca Materno-Fetal/genética , Troca Materno-Fetal/imunologia , Modelos Biológicos , Placenta/imunologia , Placenta/metabolismo , Placenta/patologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Proteinúria/imunologia , Proteinúria/metabolismo , Ratos , Transdução de Sinais
11.
Am J Reprod Immunol ; 78(2)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28585775

RESUMO

The PD-1/PD-L1 pathway plays a vital role in the maintenance of peripheral tolerance, promoting the development and function of regulatory T cells, and maintaining the quiescence of autoreactive T cells. Abnormalities in this inhibitory pathway are involved in the pathogenesis of some disorders such as tumours, autoimmune diseases, pregnancy complications, and transplantation rejection. Immune privilege represents a special immunological condition, where foreign antigens can be tolerated and do not elicit an immune response. The anterior chamber of the eye, central nervous system, testis, pregnant uterus, and hair follicles are all regarded as immune-privileged sites in humans. Numerous studies show that the PD-1/PD-L1 pathway contributes to the maintenance of the immune-privileged microenvironment. In this review, we will mainly focus on the roles of the PD-1/PD-L1 pathway in the anterior chamber of the eye, brain and testis, as well as further investigations in testis.


Assuntos
Antígeno B7-H1/imunologia , Receptor de Morte Celular Programada 1/imunologia , Animais , Encéfalo/imunologia , Olho/imunologia , Humanos , Masculino , Testículo/imunologia
12.
Am J Reprod Immunol ; 78(2)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28585734

RESUMO

The well-established classic role of vitamin D is implicated in the regulation of the balance between calcium and phosphorus. Furthermore, vitamin D is also involved in many non-classic physiological processes, mainly including the regulation of cell proliferation, differentiation, apoptosis and immune function, participation in the inflammatory response and maintenance of genome stability function. During pregnancy, vitamin D receptor and its metabolic enzymes are expressed at the placenta and decidua, indicating the potential role in the mechanism of immunomodulation at the maternal-fetal interface. The insufficiency or deficiency of vitamin D may affect the mother directly and is related to specific pregnancy outcomes, such as preeclampsia, gestational diabetes, and recurrent miscarriage. This article reviews the effects of vitamin D on immune regulation during pregnancy.


Assuntos
Gravidez/imunologia , Vitamina D/imunologia , Animais , Feminino , Humanos , Complicações na Gravidez/imunologia , Vitamina D/metabolismo
13.
Am J Reprod Immunol ; 78(2)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28251714

RESUMO

In the past decades, studies have shown that a balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells plays a major role in autoimmune/inflammatory diseases as well as pregnancy complications. Decreased number and function of Tregs, and increased number of Th17 cells which often have an opposed effect of Tregs, are associated with these conditions. Recently, the plasticity of Tregs and Th17 cells has been reported to be involved in the pathogenesis of autoimmune/inflammatory diseases. Hence, we summarize the current knowledge of Tregs and Th17 cells plasticity with an emphasis on their reciprocal transdifferentiation in autoimmune/inflammatory diseases. Moreover, the regulators of the Tregs-to-Th17 cells transdifferentiation are discussed as well. Finally, by reviewing the immuno-inflammatory status of pregnancy complications, such as preeclampsia and unexplained recurrent pregnancy losses, a possibility of Tregs-to-Th17 cells transdifferentiation as an underlying immune-pathology of these conditions is discussed.


Assuntos
Doenças Autoimunes/imunologia , Inflamação/imunologia , Complicações na Gravidez/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Transdiferenciação Celular , Feminino , Humanos , Gravidez , Linfócitos T Reguladores/fisiologia , Células Th17/fisiologia
14.
Front Immunol ; 8: 120, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28232836

RESUMO

Macrophages are a subset of mononuclear phagocytes of the innate immune system with high plasticity and heterogeneity. At the maternal-fetal interface, macrophages are present in all stages of pregnancy and involved in a variety of activities, including regulation of immune cell activities, decidualization, placental cell invasion, angiogenesis, parturition, and postpartum uterine involution. The activation state and function of uterine-placental macrophages are largely dependent on the local tissue microenvironment. However, disruption of the uterine microenvironment can have profound effects on macrophage activity and subsequently impact pregnancy outcome. Thus, appropriately and timely regulated macrophage polarization has been considered a key determinant of successful pregnancy. Targeting macrophage polarization might be an efficient strategy for maintaining maternal-fetal immune homeostasis and a normal pregnancy. Here, we will review the latest findings regarding the modulators regulating macrophage polarization in healthy pregnancies and pregnancy complications, which might provide a basis for macrophage-centered therapeutic strategies.

15.
J Reprod Immunol ; 118: 92-99, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27792886

RESUMO

Successful pregnancy relies on the accurate regulation of the maternal-fetal immune system. Without enough tolerance in the uterine microenvironment, the mother and the hemiallogeneic fetus could not peacefully coexist. T cell immunoglobulin and mucin domain (Tim)-3 is a molecule originally regarded as to be expressed on terminally differentiated IFN-γ expressing CD4+ T cells (Th1). The engagement of Tim-3 with its ligand, galectin-9 (Gal-9) could induce the exhaustion or apoptosis of effector T cells, and thus might regulate the tolerance. Tim-3 pathway also participates in regulating the activities of CD4+ regulatory T cells, monocyte-macrophages, dendritic cells and natural killer cells. Dysregulation of Tim-3 expression can elicit excessive or inhibited inflammatory responses and ultimately result in autoimmune diseases, viral or tumor evasion and pregnancy complications. In this review, we will mainly focus on the expression of Tim-3 on local immune cells and its function in pregnancy. In addition, meaningful questions that need further investigation and the potential roles of Tim-3 in fetal tolerance will be discussed. Deeper understanding of the immune checkpoint receptor Tim-3 will shed new light on exploring the pathogenesis of some pregnancy complications, including pre-eclampsia, intrauterine growth restriction, recurrent spontaneous abortion and preterm birth. Tim-3 pathway might be a new target of immune therapy for pregnancy complications in the future.


Assuntos
Aborto Habitual/imunologia , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Células Matadoras Naturais/imunologia , Pré-Eclâmpsia/imunologia , Linfócitos T Reguladores/imunologia , Animais , Feminino , Desenvolvimento Fetal , Galectinas/metabolismo , Regulação da Expressão Gênica , Receptor Celular 2 do Vírus da Hepatite A/genética , Humanos , Tolerância Imunológica , Troca Materno-Fetal/imunologia , Gravidez
16.
J Reprod Immunol ; 112: 73-80, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26340023

RESUMO

During pregnancy, the maternal immune system is challenged by the semi-allogeneic fetus, which leads to systemic and local immunity. Systemic immunity, including enhanced innate immunity with increased activation of monocytes, is induced by various placental factors. Maternal immune adaptations are most evident at the feto-maternal interface, where macrophages are enriched and communicate with various decidual leukocytes. These cells are not only contributing to the protection of the growing fetus from microorganisms, but also aiding placental development by promoting trophoblast invasion and spiral artery remodeling, and the parturition process. Thus, monocytes and macrophages concurrently play important roles throughout the trimesters. Dysregulation of these cells may thus lead to pregnancy complications, such as pre-eclampsia and preterm labor. In this review, monocytes and macrophage subsets and their roles in normal and pathological pregnancies are reviewed.


Assuntos
Macrófagos/imunologia , Monócitos/imunologia , Trabalho de Parto Prematuro/imunologia , Pré-Eclâmpsia/imunologia , Trofoblastos/imunologia , Feminino , Humanos , Macrófagos/patologia , Monócitos/patologia , Trabalho de Parto Prematuro/patologia , Pré-Eclâmpsia/patologia , Gravidez , Trofoblastos/patologia
17.
Am J Reprod Immunol ; 74(2): 116-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25850575

RESUMO

PROBLEM: We aim to investigate the proportion and absolute counts of peripheral blood monocyte subsets in women with normal pregnancy (NP) and pre-eclampsia (PE), and their correlation with the clinical manifestation and severity of PE. METHOD OF STUDY: Peripheral blood was obtained from women with NP (n = 30), mild PE (MPE, n = 15) and severe PE (SPE, n = 30). The proportion and absolute counts of CD16(+) monocytes and the subsets including intermediate (CD14(++) CD16(+) HLA-DR(+) ) and non-classical (CD14(+) CD16(++) HLA-DR(+) ) monocytes were determined by flow cytometric analysis. RESULTS: Women with MPE and SPE had significantly increased absolute count of CD14(++) CD16(+) HLA-DR(+) monocyte subsets (P < 0.01 each) as compared to NP women. In addition, there were significant differences in the absolute count of CD14(++) CD16(+) HLA-DR(+) monocyte subsets between MPE and SPE groups (P < 0.05). The proportion of CD14(++) CD16(+) HLA-DR(+) monocyte subsets was significantly increased in SPE compared to MPE and NP (P < 0.01 each). The absolute count (r = 0.332, P < 0.05) and proportion (r = 0.447, P < 0.01) of CD14(++) CD16(+) HLA-DR(+) monocytes were positively correlated with the severity of PE. Multivariate logistic regression analysis further revealed that the absolute count of CD14(++) CD16(+) HLA-DR(+) monocytes was a potential marker for PE (P < 0.01). CONCLUSION: A preferential increase in peripheral blood CD14(++) CD16(+) HLA-DR(+) monocytes is quantitatively correlated with clinical manifestation of PE.


Assuntos
Monócitos/imunologia , Pré-Eclâmpsia/imunologia , Adulto , Feminino , Proteínas Ligadas por GPI/imunologia , Antígenos HLA-DR/imunologia , Humanos , Contagem de Leucócitos , Receptores de Lipopolissacarídeos/imunologia , Gravidez , Receptores de IgG/imunologia , Adulto Jovem
18.
Reprod Sci ; 22(11): 1377-86, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25868581

RESUMO

OBJECTIVE: To establish a mouse model for endometrial injury and determine the underlying mechanism regarding its favorable effect on embryo implantation. STUDY DESIGN: Female Kunming mice were randomly allocated into 4 groups: group I, normal control; group II, injury procedure control; and group III and group IV, the mice being scratched with a blunt syringe on the right uterine horn or both, respectively. All the mice were mated with the males during the next estrus phase. The number of implanted embryos on each side of uterus was calculated on day 8 of pregnancy. The endometrial samples were taken on day 4 of pregnancy, and the local morphological changes and cytokine expressions were examined. RESULTS: Compared to group II, our results showed that in group IV (1) there were significantly higher numbers of implanted embryos, (2) the endometrial glands and vasculatures in stroma were obviously increased and the pinopodes were abundant and well developed, and (3) the local levels of cytokines leukemia inhibitory factor (LIF) and oncostatin M (OSM) messenger RNA and protein expression were significantly increased. CONCLUSIONS: Local mechanical injury on mouse uteri enhanced endometrial receptivity and improved embryo implantation, which were correlated with the characteristic changes in endometrial morphology and the upregulation of LIF and OSM gene and protein expression.


Assuntos
Citocinas/metabolismo , Implantação do Embrião , Endométrio/metabolismo , Ferimentos Penetrantes/metabolismo , Animais , Citocinas/genética , Modelos Animais de Doenças , Endométrio/lesões , Endométrio/fisiopatologia , Endométrio/ultraestrutura , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/metabolismo , Camundongos , Oncostatina M/genética , Oncostatina M/metabolismo , Gravidez , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Tempo , Regulação para Cima , Ferimentos Penetrantes/genética , Ferimentos Penetrantes/patologia , Ferimentos Penetrantes/fisiopatologia
19.
Am J Reprod Immunol ; 74(3): 201-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25640631

RESUMO

Pregnancy presents a great challenge to the maternal immune system. Given that maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to serve a central function in altering the maternal immune responses. Regulatory T cells (Tregs) and the PD-1/PD-L1 pathway are both critical in controlling the immune responses. Recent studies have proved the critical function of the PD-1/PD-L1 pathway in regulating the T-cell homeostasis and the peripheral tolerance through promoting the development and function of Tregs, and inhibiting the activation of effector T cells. The function of the PD-1/PD-L1 pathway in feto-maternal interface and pregnancy has been investigated in human and animal models of pregnancy. In this review, we provide recent insight into the role of the PD-1/PD-L1 pathway in regulating T-cell homeostasis, maternal tolerance, and pregnancy-related complications as well as its possible applicability in clinical immunotherapy.


Assuntos
Antígeno B7-H1/metabolismo , Troca Materno-Fetal/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T Reguladores/imunologia , Feminino , Humanos , Tolerância Imunológica/imunologia , Gravidez , Transdução de Sinais/imunologia , Linfócitos T Reguladores/metabolismo
20.
Am J Reprod Immunol ; 70(6): 454-63, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24033608

RESUMO

PROBLEM: The objective of this study was to determine the simultaneous changes and the correlation between circulating regulatory T (Tregs) and B-cell subsets in normal pregnancy (NP) and pre-eclampsia (PE). Meanwhile, the regulatory function of Tregs on B-cell proliferation was evaluated in vitro. METHOD OF STUDY: A total of 32 PE and 40 NP women matched for age, gestational age, and parity were included. Using flow cytometry, the percentages of peripheral blood Tregs and B-cell subsets were determined. Moreover, the regulatory function of Tregs on autologous B-cell proliferation in PE and NP was investigated in vitro by flow cytometry and analyzed by modfit software. RESULTS: The proportions (%) of CD4(+)  Foxp3(+) (P < 0.001) and CD4(+)  CD25(+)  Foxp3(+) (P < 0.01) cells within total CD4(+) T cells were significantly decreased in PE as compared to those of NP. However, no difference was found in CD4(+)  CD25(+) cells in CD4(+) T cell population. CD19(+)  CD27(+) (P < 0.05) and CD19(+)  CD27(+)  IgD(+) (P < 0.01) B cells within CD19(+) B cells (%) in PE were higher than those of NP. Negative correlations between the percentage of CD4(+)  CD25(+)  Foxp3(+) in CD4(+) T cells and that of CD19(+)  CD27(+) (r = -0.384, P < 0.05) and CD19(+)  CD27(+)  IgD(+) (r = -0.402, P < 0.05) in CD19(+) B cells were present in PE but not in NP. Furthermore, the in vitro study demonstrated a significant increase in B-cell proliferation in PE as compared to NP. Tregs in PE were able to suppress the proliferation and precursor frequency of autologous B cells (P < 0.05 each). CONCLUSION: The study indicates that a negative correlation between Tregs and memory B cells is present in women with PE, characterized by a systemic decrease in Tregs and an increase in memory B cells. Although the quantitative deficit of Tregs is present in PE, the Tregs still have a suppressive role in autologous B-cell proliferation.


Assuntos
Linfócitos B/citologia , Linfócitos B/imunologia , Memória Imunológica/imunologia , Pré-Eclâmpsia/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Proliferação de Células , Feminino , Humanos , Pré-Eclâmpsia/patologia , Gravidez , Estudos Prospectivos
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