The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Maria Cristina Mingari - One of the best experts on this subject based on the ideXlab platform.
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unique eomes nk cell subsets are present in uterus and Decidua during early pregnancy
Frontiers in Immunology, 2016Co-Authors: Elisa Montaldo, Paola Vacca, Laura Chiossone, Daniele Croxatto, Fabrizio Loiacono, Stefania Martini, Simone Ferrero, Thierry Walzer, Lorenzo Moretta, Maria Cristina MingariAbstract:Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and Decidua express Eomesodermin (Eomes), thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells. In humans, Eomes(+) Decidual NK (dNK) cells express CD49a and other markers of tissue residency, including CD103, integrin β7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNγ-producing Eomes(+) NK cells. We show that TGFβ can sustain/induce CD103 and CD9 expression in dNK cells and Decidual CD34-derived NK cells, indicating that the Decidual microenvironment can instruct the phenotype of Eomes(+) NK cells. In murine Decidua and uterus, Eomes(+) cells include CD49a(-)CD49b(+) conventional NK cells and CD49a(+) cells. Notably, Eomes(+)CD49a(+) cells are absent in spleen and liver. Decidual and uterine Eomes(+)CD49a(+) cells can be dissected in two peculiar cell subsets according to CD49b expression. CD49a(+)CD49b ((-)) and CD49a(+)CD49b(+) cells are enriched in immature CD11b(low)CD27(high) cells, while CD49a(-)CD49b(+) cells contain higher percentages of mature CD11b(high)CD27(low) cells, both in uterus and Decidua. Moreover, Eomes(+)CD49a(+)CD49b(-) cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes(-)CD49a(+) ILC1 population present in Decidua and uterus increases during pregnancy. CD49b(-)Eomes(±) cells produce mainly TNF, while CD49a(-)CD49b(+) conventional NK cells and CD49a(+)CD49b(+) cells produce both IFNγ and TNF. Thus, human and murine Decidua contains unique subsets of group 1 ILCs, including Eomes(+) and Eomes(-) cells, with peculiar phenotypic and functional features. Our study contributes to re-examination of the complexity of uterine and Decidual ILC subsets in humans and mice and highlights the role of the Decidual microenvironment in shaping the features of these cells.
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Unique Eomes(+) NK Cell Subsets Are Present in Uterus and Decidua During Early Pregnancy
Frontiers in Immunology, 2015Co-Authors: Elisa Montaldo, Paola Vacca, Laura Chiossone, Daniele Croxatto, Fabrizio Loiacono, Stefania Martini, Simone Ferrero, Thierry Walzer, Lorenzo Moretta, Maria Cristina MingariAbstract:Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and Decidua express Eomesodermin (Eomes), thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells. In humans, Eomes(+) Decidual NK (dNK) cells express CD49a and other markers of tissue residency, including CD103, integrin β7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNγ-producing Eomes(+) NK cells. We show that TGFβ can sustain/induce CD103 and CD9 expression in dNK cells and Decidual CD34-derived NK cells, indicating that the Decidual microenvironment can instruct the phenotype of Eomes(+) NK cells. In murine Decidua and uterus, Eomes(+) cells include CD49a(-)CD49b(+) conventional NK cells and CD49a(+) cells. Notably, Eomes(+)CD49a(+) cells are absent in spleen and liver. Decidual and uterine Eomes(+)CD49a(+) cells can be dissected in two peculiar cell subsets according to CD49b expression. CD49a(+)CD49b ((-)) and CD49a(+)CD49b(+) cells are enriched in immature CD11b(low)CD27(high) cells, while CD49a(-)CD49b(+) cells contain higher percentages of mature CD11b(high)CD27(low) cells, both in uterus and Decidua. Moreover, Eomes(+)CD49a(+)CD49b(-) cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes(-)CD49a(+) ILC1 population present in Decidua and uterus increases during pregnancy. CD49b(-)Eomes(\textpm) cells produce mainly TNF, while CD49a(-)CD49b(+) conventional NK cells and CD49a(+)CD49b(+) cells produce both IFNγ and TNF. Thus, human and murine Decidua contains unique subsets of group 1 ILCs, including Eomes(+) and Eomes(-) cells, with peculiar phenotypic and functional features. Our study contributes to re-examination of the complexity of uterine and Decidual ILC subsets in humans and mice and highlights the role of the Decidual microenvironment in shaping the features of these cells.
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cd34 hematopoietic precursors are present in human Decidua and differentiate into natural killer cells upon interaction with stromal cells
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Paola Vacca, Elisa Montaldo, Lorenzo Moretta, Chiara Vitale, Romana Conte, Claudia Cantoni, E Fulcheri, Valeria Darretta, Maria Cristina MingariAbstract:Natural killer (NK) cells are the main lymphoid population in the maternal Decidua during the first trimester of pregnancy. Decidual NK (dNK) cells display a unique functional profile and play a key role in promoting tissue remodeling, neoangiogenesis, and immune modulation. However, little information exists on their origin and development. Here we discovered CD34+ hematopoietic precursors in human Decidua (dCD34+). We show that dCD34+ cells differ from cord blood- or peripheral blood-derived CD34+ precursors. The expression of IL-15/IL-2 receptor common β-chain (CD122), IL-7 receptor α-chain (CD127), and mRNA for E4BP4 and ID2 transcription factors suggested that dCD34+ cells are committed to the NK cell lineage. Moreover, they could undergo in vitro differentiation into functional (i.e., IL-8– and IL-22–producing) CD56brightCD16−KIR+/− NK cells in the presence of growth factors or even upon coculture with Decidual stromal cells. Their NK cell commitment was further supported by the failure to undergo myeloid differentiation in the presence of GM-CSF. Our findings strongly suggest that Decidual NK cells may directly derive from CD34+ cell precursors present in the Decidua upon specific cellular interactions with components of the Decidual microenvironment.
Elisa Montaldo - One of the best experts on this subject based on the ideXlab platform.
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unique eomes nk cell subsets are present in uterus and Decidua during early pregnancy
Frontiers in Immunology, 2016Co-Authors: Elisa Montaldo, Paola Vacca, Laura Chiossone, Daniele Croxatto, Fabrizio Loiacono, Stefania Martini, Simone Ferrero, Thierry Walzer, Lorenzo Moretta, Maria Cristina MingariAbstract:Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and Decidua express Eomesodermin (Eomes), thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells. In humans, Eomes(+) Decidual NK (dNK) cells express CD49a and other markers of tissue residency, including CD103, integrin β7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNγ-producing Eomes(+) NK cells. We show that TGFβ can sustain/induce CD103 and CD9 expression in dNK cells and Decidual CD34-derived NK cells, indicating that the Decidual microenvironment can instruct the phenotype of Eomes(+) NK cells. In murine Decidua and uterus, Eomes(+) cells include CD49a(-)CD49b(+) conventional NK cells and CD49a(+) cells. Notably, Eomes(+)CD49a(+) cells are absent in spleen and liver. Decidual and uterine Eomes(+)CD49a(+) cells can be dissected in two peculiar cell subsets according to CD49b expression. CD49a(+)CD49b ((-)) and CD49a(+)CD49b(+) cells are enriched in immature CD11b(low)CD27(high) cells, while CD49a(-)CD49b(+) cells contain higher percentages of mature CD11b(high)CD27(low) cells, both in uterus and Decidua. Moreover, Eomes(+)CD49a(+)CD49b(-) cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes(-)CD49a(+) ILC1 population present in Decidua and uterus increases during pregnancy. CD49b(-)Eomes(±) cells produce mainly TNF, while CD49a(-)CD49b(+) conventional NK cells and CD49a(+)CD49b(+) cells produce both IFNγ and TNF. Thus, human and murine Decidua contains unique subsets of group 1 ILCs, including Eomes(+) and Eomes(-) cells, with peculiar phenotypic and functional features. Our study contributes to re-examination of the complexity of uterine and Decidual ILC subsets in humans and mice and highlights the role of the Decidual microenvironment in shaping the features of these cells.
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Unique Eomes(+) NK Cell Subsets Are Present in Uterus and Decidua During Early Pregnancy
Frontiers in Immunology, 2015Co-Authors: Elisa Montaldo, Paola Vacca, Laura Chiossone, Daniele Croxatto, Fabrizio Loiacono, Stefania Martini, Simone Ferrero, Thierry Walzer, Lorenzo Moretta, Maria Cristina MingariAbstract:Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and Decidua express Eomesodermin (Eomes), thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells. In humans, Eomes(+) Decidual NK (dNK) cells express CD49a and other markers of tissue residency, including CD103, integrin β7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNγ-producing Eomes(+) NK cells. We show that TGFβ can sustain/induce CD103 and CD9 expression in dNK cells and Decidual CD34-derived NK cells, indicating that the Decidual microenvironment can instruct the phenotype of Eomes(+) NK cells. In murine Decidua and uterus, Eomes(+) cells include CD49a(-)CD49b(+) conventional NK cells and CD49a(+) cells. Notably, Eomes(+)CD49a(+) cells are absent in spleen and liver. Decidual and uterine Eomes(+)CD49a(+) cells can be dissected in two peculiar cell subsets according to CD49b expression. CD49a(+)CD49b ((-)) and CD49a(+)CD49b(+) cells are enriched in immature CD11b(low)CD27(high) cells, while CD49a(-)CD49b(+) cells contain higher percentages of mature CD11b(high)CD27(low) cells, both in uterus and Decidua. Moreover, Eomes(+)CD49a(+)CD49b(-) cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes(-)CD49a(+) ILC1 population present in Decidua and uterus increases during pregnancy. CD49b(-)Eomes(\textpm) cells produce mainly TNF, while CD49a(-)CD49b(+) conventional NK cells and CD49a(+)CD49b(+) cells produce both IFNγ and TNF. Thus, human and murine Decidua contains unique subsets of group 1 ILCs, including Eomes(+) and Eomes(-) cells, with peculiar phenotypic and functional features. Our study contributes to re-examination of the complexity of uterine and Decidual ILC subsets in humans and mice and highlights the role of the Decidual microenvironment in shaping the features of these cells.
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cd34 hematopoietic precursors are present in human Decidua and differentiate into natural killer cells upon interaction with stromal cells
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Paola Vacca, Elisa Montaldo, Lorenzo Moretta, Chiara Vitale, Romana Conte, Claudia Cantoni, E Fulcheri, Valeria Darretta, Maria Cristina MingariAbstract:Natural killer (NK) cells are the main lymphoid population in the maternal Decidua during the first trimester of pregnancy. Decidual NK (dNK) cells display a unique functional profile and play a key role in promoting tissue remodeling, neoangiogenesis, and immune modulation. However, little information exists on their origin and development. Here we discovered CD34+ hematopoietic precursors in human Decidua (dCD34+). We show that dCD34+ cells differ from cord blood- or peripheral blood-derived CD34+ precursors. The expression of IL-15/IL-2 receptor common β-chain (CD122), IL-7 receptor α-chain (CD127), and mRNA for E4BP4 and ID2 transcription factors suggested that dCD34+ cells are committed to the NK cell lineage. Moreover, they could undergo in vitro differentiation into functional (i.e., IL-8– and IL-22–producing) CD56brightCD16−KIR+/− NK cells in the presence of growth factors or even upon coculture with Decidual stromal cells. Their NK cell commitment was further supported by the failure to undergo myeloid differentiation in the presence of GM-CSF. Our findings strongly suggest that Decidual NK cells may directly derive from CD34+ cell precursors present in the Decidua upon specific cellular interactions with components of the Decidual microenvironment.
Frans H.j. Claas - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Macrophage Phenotype Between Decidua Basalis and Decidua Parietalis by Flow Cytometry
Placenta, 2008Co-Authors: U. Repnik, Tamara Tilburgs, Dave L. Roelen, B.j. Van Der Mast, H. H. H. Kanhai, S.a. Scherjon, Frans H.j. ClaasAbstract:The two regions of the maternal Decidua, Decidua basalis and Decidua parietalis, differ in the extent of trophoblast invasion and consequently in cytokines and other biological mediators, extracellular matrix and cellular components. Our aim was to compare the phenotypic features of macrophages from the two Decidual regions across a broad gestational age range. We isolated macrophages by enzymatic digestion from healthy Decidua samples obtained after elective abortions, at 9-18-week and at 19-23-weeks, or after term deliveries (caesarean sections at term and spontaneous term vaginal deliveries). Macrophages were analysed by flow cytometry applying the same instrument settings to all the samples to allow semi-quantitative comparison of the expression of a particular marker between different samples. We found higher expressions of CD80, CD86 and HLA-DR, suggestive of a more activated phenotype of Decidual macrophages, at early/mid pregnancy than at term. Marginal differences were found between term Decidual macrophages obtained after spontaneous vaginal deliveries or caesarean sections which imply that the parturient process is not associated with Decidual macrophage activation. The expressions of CD105, DC-SIGN and MMR were the strongest in Decidua basalis of mid pregnancy and indicate the importance of Decidual macrophages in tissue homeostasis at the uteroplacental interface.
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Increased T-cell activation in Decidua parietalis compared to Decidua basalis in uncomplicated human term pregnancy.
American journal of reproductive immunology (New York N.Y. : 1989), 2003Co-Authors: Aliana P Sindram-trujillo, Dave L. Roelen, Sicco A. Scherjon, Humphrey H.h. Kanhai, Frans H.j. ClaasAbstract:PROBLEM: The aim of this study was to quantify and compare activated T cells in term Decidua basalis and parietalis using flow cytometry. METHOD OF STUDY: Term Decidua basalis and parietalis samples were obtained from 20 placentas collected after elective caesarean section. Percentages of leukocyte subclasses within the CD45+ cell fraction and activated T cells were determined by flow cytometry. RESULTS: There was no significant difference in CD45+, CD14+, CD19+, and CD3+ cell percentages. However, within the CD3+ population, there were significantly more T-cell receptor-γδ+ (TCR-γδ+) and CD8+ cells in Decidua parietalis compared with Decidua basalis. More importantly, percentages of T cells expressing CD25, human leukocyte antigen (HLA)-DR, CD45RO, and CD69 markers were significantly increased in Decidua parietalis. CONCLUSION: These findings suggest that there are more activated T cells in Decidua parietalis than in Decidua basalis. Further investigation into differences between the two Decidual sites may expand our understanding of the immunology of the maternal–fetal interface.
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Differential distribution of NK cells in Decidua basalis compared with Decidua parietalis after uncomplicated human term pregnancy.
Human immunology, 2003Co-Authors: Aliana P Sindram-trujillo, Dave L. Roelen, Sicco A. Scherjon, Humphrey H.h. Kanhai, Paula P Van Hulst-van Miert, Jolien J. Van Der Ploeg-van Schip, Frans H.j. ClaasAbstract:As pregnancy progresses, a characteristic decline in the percentage of CD56bright CD16− uterine natural killer (NK) cells occurs. Studies of term Decidua, however, have focused only on leukocytes derived from Decidua basalis, the site of implantation. The Decidua parietalis, lining the remainder of the uterine cavity is another important region of the maternal-fetal interface that forms contact with fetal tissue at the end of the first trimester. The aim of this study was to evaluate possible differences in expression of CD16 and CD56 on leukocytes from normal term Decidua basalis and Decidua parietalis. Decidua basalis and parietalis samples were obtained from 30 placentas collected after elective cesarean section. Percentages of leukocyte subpopulations and NK cell subsets within the CD45+ cell fraction were determined by flow cytometry. In six Decidual samples, concurrent immunohistochemical staining was performed. Higher percentages of CD56dim CD16+ NK cells and CD56− CD16+ cells were found in Decidua basalis in comparison to Decidua parietalis. In contrast, the percentage of CD56bright CD16− uterine NK cells was significantly higher in Decidua parietalis. Immunohistochemical quantification supported flow cytometric results. We conclude that significant differences exist with respect to the distribution of NK cells in term Decidua basalis and parietalis. Future functional studies may improve our understanding of their role at the maternal-fetal interface.
Paola Vacca - One of the best experts on this subject based on the ideXlab platform.
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unique eomes nk cell subsets are present in uterus and Decidua during early pregnancy
Frontiers in Immunology, 2016Co-Authors: Elisa Montaldo, Paola Vacca, Laura Chiossone, Daniele Croxatto, Fabrizio Loiacono, Stefania Martini, Simone Ferrero, Thierry Walzer, Lorenzo Moretta, Maria Cristina MingariAbstract:Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and Decidua express Eomesodermin (Eomes), thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells. In humans, Eomes(+) Decidual NK (dNK) cells express CD49a and other markers of tissue residency, including CD103, integrin β7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNγ-producing Eomes(+) NK cells. We show that TGFβ can sustain/induce CD103 and CD9 expression in dNK cells and Decidual CD34-derived NK cells, indicating that the Decidual microenvironment can instruct the phenotype of Eomes(+) NK cells. In murine Decidua and uterus, Eomes(+) cells include CD49a(-)CD49b(+) conventional NK cells and CD49a(+) cells. Notably, Eomes(+)CD49a(+) cells are absent in spleen and liver. Decidual and uterine Eomes(+)CD49a(+) cells can be dissected in two peculiar cell subsets according to CD49b expression. CD49a(+)CD49b ((-)) and CD49a(+)CD49b(+) cells are enriched in immature CD11b(low)CD27(high) cells, while CD49a(-)CD49b(+) cells contain higher percentages of mature CD11b(high)CD27(low) cells, both in uterus and Decidua. Moreover, Eomes(+)CD49a(+)CD49b(-) cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes(-)CD49a(+) ILC1 population present in Decidua and uterus increases during pregnancy. CD49b(-)Eomes(±) cells produce mainly TNF, while CD49a(-)CD49b(+) conventional NK cells and CD49a(+)CD49b(+) cells produce both IFNγ and TNF. Thus, human and murine Decidua contains unique subsets of group 1 ILCs, including Eomes(+) and Eomes(-) cells, with peculiar phenotypic and functional features. Our study contributes to re-examination of the complexity of uterine and Decidual ILC subsets in humans and mice and highlights the role of the Decidual microenvironment in shaping the features of these cells.
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Unique Eomes(+) NK Cell Subsets Are Present in Uterus and Decidua During Early Pregnancy
Frontiers in Immunology, 2015Co-Authors: Elisa Montaldo, Paola Vacca, Laura Chiossone, Daniele Croxatto, Fabrizio Loiacono, Stefania Martini, Simone Ferrero, Thierry Walzer, Lorenzo Moretta, Maria Cristina MingariAbstract:Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and Decidua express Eomesodermin (Eomes), thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells. In humans, Eomes(+) Decidual NK (dNK) cells express CD49a and other markers of tissue residency, including CD103, integrin β7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNγ-producing Eomes(+) NK cells. We show that TGFβ can sustain/induce CD103 and CD9 expression in dNK cells and Decidual CD34-derived NK cells, indicating that the Decidual microenvironment can instruct the phenotype of Eomes(+) NK cells. In murine Decidua and uterus, Eomes(+) cells include CD49a(-)CD49b(+) conventional NK cells and CD49a(+) cells. Notably, Eomes(+)CD49a(+) cells are absent in spleen and liver. Decidual and uterine Eomes(+)CD49a(+) cells can be dissected in two peculiar cell subsets according to CD49b expression. CD49a(+)CD49b ((-)) and CD49a(+)CD49b(+) cells are enriched in immature CD11b(low)CD27(high) cells, while CD49a(-)CD49b(+) cells contain higher percentages of mature CD11b(high)CD27(low) cells, both in uterus and Decidua. Moreover, Eomes(+)CD49a(+)CD49b(-) cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes(-)CD49a(+) ILC1 population present in Decidua and uterus increases during pregnancy. CD49b(-)Eomes(\textpm) cells produce mainly TNF, while CD49a(-)CD49b(+) conventional NK cells and CD49a(+)CD49b(+) cells produce both IFNγ and TNF. Thus, human and murine Decidua contains unique subsets of group 1 ILCs, including Eomes(+) and Eomes(-) cells, with peculiar phenotypic and functional features. Our study contributes to re-examination of the complexity of uterine and Decidual ILC subsets in humans and mice and highlights the role of the Decidual microenvironment in shaping the features of these cells.
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cd34 hematopoietic precursors are present in human Decidua and differentiate into natural killer cells upon interaction with stromal cells
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Paola Vacca, Elisa Montaldo, Lorenzo Moretta, Chiara Vitale, Romana Conte, Claudia Cantoni, E Fulcheri, Valeria Darretta, Maria Cristina MingariAbstract:Natural killer (NK) cells are the main lymphoid population in the maternal Decidua during the first trimester of pregnancy. Decidual NK (dNK) cells display a unique functional profile and play a key role in promoting tissue remodeling, neoangiogenesis, and immune modulation. However, little information exists on their origin and development. Here we discovered CD34+ hematopoietic precursors in human Decidua (dCD34+). We show that dCD34+ cells differ from cord blood- or peripheral blood-derived CD34+ precursors. The expression of IL-15/IL-2 receptor common β-chain (CD122), IL-7 receptor α-chain (CD127), and mRNA for E4BP4 and ID2 transcription factors suggested that dCD34+ cells are committed to the NK cell lineage. Moreover, they could undergo in vitro differentiation into functional (i.e., IL-8– and IL-22–producing) CD56brightCD16−KIR+/− NK cells in the presence of growth factors or even upon coculture with Decidual stromal cells. Their NK cell commitment was further supported by the failure to undergo myeloid differentiation in the presence of GM-CSF. Our findings strongly suggest that Decidual NK cells may directly derive from CD34+ cell precursors present in the Decidua upon specific cellular interactions with components of the Decidual microenvironment.
Ulrike Kammerer - One of the best experts on this subject based on the ideXlab platform.
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quantification of the predominant immune cell populations in Decidua throughout human pregnancy
American Journal of Reproductive Immunology, 2014Co-Authors: Catharina Bartmann, Michaela Kapp, S E Segerer, Lorenz Rieger, Marc Sutterlin, Ulrike KammererAbstract:Problem To date, a multiplicity of factors contributing to the establishment and progression of a successful pregnancy have been postulated. There is emerging evidence that Decidual leukocytes could be decisive factors during pregnancy. Despite numerous investigations on immune cells in human early pregnancy Decidua, little is known about the physiological composition and proportion of the various immune cell populations during the different phases of pregnancy. In this study, we therefore analyzed the proportion of the dominant Decidual leukocytes in human tissue samples derived from all phases of pregnancy. Methods Single cell suspensions were prepared from Decidual samples from 205 patients at 6–40 weeks of gestation. Cell populations were analyzed by flow cytometry, and immune cell populations were quantified as percentage of Decidual CD45+ cells. Results There was generally no difference in immune cell counts comparing Decidua of healthy gestations and those with systemic inflammation. Overall, the proportion of uNK cells continuously decreased, while the amount of monocytes, immature dendritic cells, and T cells increased until term. Striking modifications in cell counts were seen during the 7th week compared with the 6th and later weeks of gestation. Conclusion Studying the proportion of Decidual immune cells during pregnancy, we detected a unique pattern which could be useful to design novel therapies for pathological conditions during pregnancy.
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human Decidua and invasive trophoblasts are rich sources of nearly all human matrix metalloproteinases
Molecular Human Reproduction, 2011Co-Authors: Jelena Anacker, Michaela Kapp, S E Segerer, Carsten Hagemann, Sonja Feix, Renate Bausch, Ulrike KammererAbstract:Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. As for all invasive cell types, the ability of CTB to infiltrate the uterine wall is facilitated by the activity of matrix metallopro- teinases (MMPs), which is regulated by tissue inhibitors of MMPs (TIMPs). There is evidence for the expression of several MMPs and TIMPs in Decidua. However, published data are limited. Therefore, to set a foundation for future research, we screened a panel of healthy human Deciduas obtained during first, second and third trimester of pregnancy in addition to isolated Decidual cell populations for the expression of all known human MMPs and TIMPs by RT- PCR, western blot and immunohistochemistry. In the Decidual samples, we detected almost all MMPs and all four TIMPs at mRNA level. While the expression of proMMP-3 and active MMP-13 and -23 was down-regulated in the course of pregnancy, the pro forms of MMP-8, -19 and -23, active MMP-9, -10, -12, -15, -16, -26 and -28, and pro- and active MMP-14 increased towards the end of gestation. All MMPs and TIMPs were expressed in uterine natural killer cells, Decidual fibroblasts and/or trophoblasts, with the exception of MMP-20 and -25. In summary, a remarkably broad spectrum of MMPs was expressed at the human feto-maternal interface, reflecting the highly invasive and remodelling effect on placenta formation. It can be speculated that expression of MMPs correlates with the invasive potential of CTBs together with a crucial role in activation of labour at term.
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profiling chemokines cytokines and growth factors in human early pregnancy Decidua by protein array
American Journal of Reproductive Immunology, 2007Co-Authors: Sabine Engert, Michaela Kapp, J Dietl, Lorenz Rieger, Jurgen C Becker, Ulrike KammererAbstract:Problem In human Decidua, a significant increase of leukocytes including CD56++CD16– uterine natural killer (uNK) cells and CD14+ monocytes has been observed with the onset of pregnancy. The mechanisms required for the recruitment of those cells to the uterus are still under debate. Cytokines and chemokines have been suggested as key factors for the regulation of these complex cellular migration and interaction processes. Method of study Investigation of the expression patterns of cytokines, chemokines and growth factors in human Decidual tissue (7–8 weeks of gestation) was performed by protein array analysis. Isolated Decidual leukocytes, i.e. CD56++CD16– uNK, CD14+ monocytes as well as cytotrophoblast (CTB) and stromal cells were tested separately. Results This analysis revealed the production of monocyte attracting chemokines (GRO, MCP-1), angiogenetic substances (EGF, VEGF, Angiogenin) as well as granulocyte activating peptides (ENA-78, IL-1β, RANTES, IL-8) by Decidual tissue and its cell subsets. Conclusion The observed pattern supports the role of Decidua as a tissue which promotes angiogenesis, attracts monocytes and modulates the function of the latter.
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unique appearance of proliferating antigen presenting cells expressing dc sign cd209 in the Decidua of early human pregnancy
American Journal of Pathology, 2003Co-Authors: Ulrike Kammerer, Andreas O Eggert, Michaela Kapp, Alexander D Mclellan, Teunis B H Geijtenbeek, J Dietl, Yvette Van Kooyk, Eckhart KampgenAbstract:Intact human pregnancy can be regarded as an immunological paradox in that the maternal immune system accepts the allogeneic embryo without general immunosuppression. Because dendritic cell (DC) subsets could be involved in peripheral tolerance, the uterine mucosa (Decidua) was investigated for DC populations. Here we describe the detailed immunohistochemical and functional characterization of HLA-DR-positive antigen-presenting cells (APCs) in early pregnancy Decidua. In contrast to classical macrophages and CD83+ DCs, which were found in comparable numbers in Decidua and nonpregnant endometrium, only Decidua harbored a significant population of HLA-DR+/DC-SIGN+ APCs further phenotyped as CD14+/CD4+/CD68+/−/CD83−/CD25−. These cells exhibited a remarkable proliferation rate (9.2 to 9.8% of all CD209+ cells) by double staining with Ki67 and proliferating cell nuclear antigen. Unique within the DC-family, the majority of DC-SIGN+ Decidual APCs were observed in situ to have intimate contact with CD56+/CD16−/ICAM-3+ Decidual natural killer cells, another pregnancy-restricted cell population. In vitro, freshly isolated CD14+/DC-SIGN+ Decidual cells efficiently took up antigen, but could not stimulate naive allogeneic T cells at all. Treatment with an inflammatory cytokine cocktail resulted in down-regulation of antigen uptake capacity and evolving capacity to effectively stimulate resting T cells. Fluorescence-activated cell sorting analysis confirmed the maturation of CD14+/DC-SIGN+ Decidual cells into CD25+/CD83+ mature DCs. In summary, this is the first identification of a uterine immature DC population expressing DC-SIGN, that appears only in pregnancy-associated tissue, has a high proliferation rate, and a conspicuous association with a natural killer subset.
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human Decidua contains potent immunostimulatory cd83 dendritic cells
American Journal of Pathology, 2000Co-Authors: Ulrike Kammerer, Michaela Kapp, Alexander D Mclellan, Eckhart Kampgen, Michael Schoppet, Hansiko Huppertz, J DietlAbstract:Dendritic cells (DCs) are sentinel cells of the immune system important in initiating antigen-specific T-cell responses to microbial and transplantation antigens. DCs are particularly found in surface tissues such as skin and mucosa, where the organism is threatened by infectious agents. The human Decidua, despite its proposed immunosuppressive function, hosts a variety of immunocompetent CD45 cells such as natural killer cells, macrophages, and T cells. Here we describe the detection, isolation, and characterization of CD45 + , CD40 + , HLA-DR ++ , and CD83 + cells from human early pregnancy Decidua with typical DC morphology. CD83 + as well as CD1a + cells were found in close vicinity to endometrial glands, with preference to the basal layer of the Decidua. In vitro , Decidual CD83 + cells could be enriched to ∼30%, with the remainder of cells encompassing DC-bound CD3 + T cells. Stimulation of allogeneic T cells in a mixed leukocyte reaction by the Decidual cell fraction enriched for CD83 + cells, was similar to that obtained with blood monocyte-derived DCs, demonstrating the potent immunostimulatory capacity of these cells. Decidual DCs with morphological, phenotypic, and functional characteristics of immunostimulatory DCs might be important mediators in the regulation of immunological balance between maternal and fetal tissue, leading to successful pregnancy.
