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Immune Regulation At The Fetalmaternal Interface With Focus On Decidual Macrophages
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Author :Judit Svensson?Arvelund Publisher :Linköping University Electronic Press ISBN 13 :9175191172 Total Pages :150 pages Book Rating :4.1/5 (751 download)
Book Synopsis Immune regulation at the fetal?maternal interface with focus on decidual macrophages by : Judit Svensson?Arvelund
Download or read book Immune regulation at the fetal?maternal interface with focus on decidual macrophages written by Judit Svensson?Arvelund and published by Linköping University Electronic Press. This book was released on 2015-04-21 with total page 150 pages. Available in PDF, EPUB and Kindle. Book excerpt: A successful pregnancy requires that the maternal immune system adapts to tolerate the semi-allogeneic fetal-placental unit. This adaptation mainly occurs locally, i.e. at the fetal-maternal interface, where fetal-derived tissues come into close contact with maternal cells in the uterine endometrium (called decidua during pregnancy). Macrophages and regulatory T (Treg) cells are maternal immune cells that are enriched in the decidua and they likely play a central role in promoting fetal tolerance. However, the precise function of decidual macrophages and the factors regulating both macrophages and Treg cells in humans are unknown. The aim of this thesis was to characterize the phenotype and function of decidual macrophages from first trimester human pregnancy and to identify factors responsible for inducing tolerogenic properties in both decidual macrophages and Treg cells. CD14+ decidual macrophages showed characteristics of immune suppressive or homeostatic macrophages (expression of CD163, CD206 and CD209), mainly produced immunosuppressive cytokines, like IL-10 and IL-35, while levels of inflammatory cytokines, for instance IL-12 and IL-23, were low. Decidual macrophages also induced the expansion of CD25highFoxp3+ Treg cells, but not of Th1, Th2 and Th17 cells, in vitro. In addition, decidual macrophages preferentially secreted the monocyte- and Treg cell-associated chemokines CCL2 and CCL18, while Th1-, Th2- and Th17-related chemokines were produced at low levels. These results suggest that decidual macrophages contribute to create the unique decidual cell composition and a tolerogenic immune environment that is compatible with fetal development. Further, by comparing decidual macrophages with different in vitro macrophage subsets, we showed that M-CSF and IL-10, but not GM-CSF, Th1 or Th2 stimuli, induced macrophages that resemble decidual macrophages in terms of cell surface marker expression, cytokine andchemokine production and gene expression profile. First trimester placental tissue, in particular placental trophoblast cells, was identified as an important source of M-CSF and IL-10. We also demonstrated that human fetal-derived placental tissue can induce the characteristics of decidual macrophages (CD163+CD206+CD209+IL-10+CCL18+) and the selective expansion of functionally suppressive CD25highFoxp3+ Treg cells, the latter partly mediated through IL-10, TGF-? and TRAIL. The placenta also limited activation of Th cells, for instance by generally reduced cytokine production. Our data show that the placenta has a unique ability to induce tolerogenic immune cells with a reduced inflammatory potential, which is essential for maintaining tissue integrity and preventing inflammation-induced fetal loss.
Book Synopsis Immune Regulation at the FetalÃØÂÂMaternal Interface with Focus on Decidual Macrophages by : Judit SvenssonâÂÂArvelund
Download or read book Immune Regulation at the FetalÃØÂÂMaternal Interface with Focus on Decidual Macrophages written by Judit SvenssonâÂÂArvelund and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Immune regulation at the foetal-maternal interface; implications for healthy and complicated pregnancies by : Robert Lindau
Download or read book Immune regulation at the foetal-maternal interface; implications for healthy and complicated pregnancies written by Robert Lindau and published by Linköping University Electronic Press. This book was released on 2020-11-10 with total page 66 pages. Available in PDF, EPUB and Kindle. Book excerpt: For a successful pregnancy, the maternal immune system must acquire tolerance towards the paternal antigens present in the semi-allogeneic foetus. This tolerance is mainly established locally at the foetal-maternal interface, where foetally-derived trophoblasts invade the maternal endometrium (called decidua during pregnancy) and come in close proximity to maternal immune cells. The decidua is populated by maternal immune cells of a unique composition, characterised by their suppressive phenotypes that are essential for maintaining tissue homeostasis. Accordingly, failure of immune tolerance can lead to pregnancy complications. Macrophages and regulatory T-cells are enriched in the decidua and are believed to play important roles in the establishment of tolerance. However, there is limited information regarding the factors that regulate their functions and if their function is compromised in pregnancy complications. The aim of this thesis was to further elucidate which factors are responsible for induction of the regulatory phenotypes of macrophages and T-cells found in the decidua, how tissue resident cells in the decidua contribute to this and if this system is compromised during pregnancy complications, such as preeclampsia and recurrent pregnancy loss. Decidual stromal cells (DSCs) constitute the largest population of tissue resident cells in the decidua. In an in vitro system of macrophage differentiation, we found that Isolated peripheral blood monocytes cultured in conditioned medium (CM) from DSCs acquired a high expression of the regulatory M2 markers CD163, CD209 and CD14, and a low expression of CD86, characteristics of decidual macrophages. This induction was in part mediated by macrophage-colony stimulating factor (M-CSF), as neutralising its effects reduced the expression of CD163. However, since only a partial reduction was reached, other factors are involved. Another likely candidate for this polarisation is interleukin (IL)-34, a second ligand for the M-CSF receptor. We showed that IL-34 is expressed by both DSCs and the foetal placenta. Further, in vitro, IL-34 was able to induce macrophages with similar properties as that of M-CSF-induced macrophages, with high expression of CD163, CD209 and CD14. This was also coupled to a cytokine secretion profile similar to M-CSF-induced macrophages, with high production of IL-10, low production of tumour necrosis factor (TNF) and no production of IL-12. We found no evidence of IL-34 being aberrantly expressed in placentas from preeclamptic women. In addition to promoting induction of macrophages with a regulatory phenotype, CM from DSCs promoted expansion of Foxp3+CD25bright regulatory T (Treg) cells in an in vitro polarisation system, in a SMAD3 dependent manner. Protein profiling of DSCs revealed limited production of the Th2 related IL-13, IL-4, IL-33 and thymic stromal lymphopoietin (TSLP), as well as no production of the Th17 related IL-17A and chemokine (C-C motif) ligand (CCL) 20. Instead we found that DSCs were more prone to production of regulatory factors, such as M-CSF, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)-?, albeit with addition of the more pro-inflammatory IL-6, chemokine (C-X-C motif) ligand (CXCL) 8 and the Th1-related CXCL10. We also investigated if the placenta´s ability to induce Treg cells and regulatory M2 macrophages is compromised in women with a history of unexplained recurrent pregnancy loss (uRPL) and if the placental secreted protein profile is skewed to a pro-inflammatory response in uRPL. Using surplus materials from chorionic villous sampling (CVS), we generated CM from placental tissue taken from healthy and uRPL pregnancies and used this to polarise macrophages and T-cells in vitro. We found no difference in the ability to induce Treg cells and regulatory M2 macrophages between the healthy group and the uRPL group. Likewise, no differences in the protein profile was observed between the two groups. Taken together, our findings imply that DSCs produce a variety of factors promoting foetal tolerance by induction of Treg cells and regulatory M2 macrophages. Furthermore, we also showed that the placenta retained its ability to induce Treg cells and regulatory M2 macrophages in women with a history of uRPL. Graviditet utgör en stor utmaning för mammans immunförsvar eftersom fostret till hälften består av gener från pappan, vilket innebär att fostret bär på gener som är främmande för mammans immunförsvar. Detta betyder att mamman måste utveckla en tolerans för att förhindra en avstötningsreaktion, men samtidigt också bevara skyddet mot potentiellt farliga infektioner. Tolerans skapas främst lokalt i kontakten mellan livmoderslemhinnan (kallad decidua under graviditet) och placentan (moderkakan), där placentaceller från fostret kommer i nära kontakt med mammans immunceller. Således har dessa immunceller en central roll i att skapa tolerans. Två celltyper som är anrikade i deciduan under en graviditet är specialiserade makrofager och regulatoriska T-celler. Dock är det inte fastställt hur dessa celler får sina immundämpande egenskaper. I denna avhandling studeras hur mammans immunceller utvecklar tolerans genom kommunikation med andra celler och genom att interagera med varandra. Fokus i avhandlingen är stödjeceller, stroma-celler, i decidua, som inte bara bygger upp vävnaden utan också deltar genom produktion av tillväxtfaktorer och hormoner som bidrar till skapande av tolerans. De övergripande målen i avhandlingen var att kartlägga faktorer som styr utvecklingen av decidua-makrofager och regulatoriska T-celler, var dessa faktorer produceras och om kvinnor som utvecklat graviditetskomplikationer har en försämrad förmåga att utveckla immundämpande immunceller lokalt. I en delstudie visar vi att de stödjeceller som utgör majoriteten av alla celler i deciduan, deciduala stromaceller, har förmågan att stimulera utvecklingen av makrofager som liknar de som finns i deciduan. För utveckling av immundämpande makrofager visade det sig att tillväxtfaktorn M-CSF var en drivande faktor. Dock dämpades uttrycket endast delvis, vilket tyder på att även andra faktorer är inblandade. En av de mest troliga är IL-34, som binder till och aktiverar samma receptor som M-CSF. I en annan delstudie visade vi att IL-34 bildas både i placentan och av stromaceller i deciduan. IL-34 var, i likhet med M-CSF, också drivande i utvecklingen av makrofager som är mycket lika makrofager i deciduan. Utöver effekten på makrofagerna drev de deciduala stromacellerna även utvecklingen av regulatoriska T-celler, troligen via produktion av en annan tillväxtfaktor, TGF-?. Då IL-34 och M-CSF var involverade i utveckling av tolerans hos makrofager, undersökte vi även om havandeskapsförgiftning (preeklampsi) var associerad med en försämrad förmåga att producera dessa faktorer i placentan. Dock hittade vi inga skillnader i förekomst av IL-34 och M-CSF hos placenta-celler från kvinnor med havandeskapsförgiftning. Sammantaget visar våra studier att deciduala stromaceller är viktiga för att producera en repertoar av faktorer som skapar och bibehåller immundämpande egenskaper hos makrofager och regulatoriska T-celler under en graviditet. Vi visar att M-CSF, IL-34 och TGF-? är centrala för denna toleransutveckling och att de bildas av deciduala stromaceller. Dock verkar dessa faktorer inte vara avvikande vid havandeskapsförgiftning
Book Synopsis Local Immune Regulation in Human Pregnancy by : Charlotte Gustafsson
Download or read book Local Immune Regulation in Human Pregnancy written by Charlotte Gustafsson and published by . This book was released on 2007 with total page 68 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Reproductive Immunology by : Gil Mor
Download or read book Reproductive Immunology written by Gil Mor and published by Academic Press. This book was released on 2021-02-12 with total page 462 pages. Available in PDF, EPUB and Kindle. Book excerpt: Reproductive Immunology: Basic Concepts gives a holistic insight into the understanding of the complex interactions between the maternal immune system and the fetal/placental unit necessary for the success of pregnancy. This interaction is critical for the support of the human fetal semiallograft and the protection against infections. The book covers various topics such as B cells, macrophages, T cells, discussion on fetal signals and their impact on maternal reproductive cells such as endometrial cells, mast cells, and the role of fetal Hofbauer cells, the immune regulatory role of glucorticoids, and many other novel topics within the field of reproductive immunology. Edited and written by experts in the field, this book introduces the up-to-date knowledge of the role of the immune system during pregnancy and provides the necessary background to understand pregnancy complications associated with alterations in the functioning of the immune system. The book provides a complete discussion on the immunological aspects of pregnancy and serves as a great tool for research scientists, students, reproductive immunologists and OBGYNs. - Shows the detailed evaluation of the knowledge related to each immune cell type in the pregnant and not pregnant uterus - Evaluates each immune cell type and its function during specific reproductive events - Provides the biological background for understanding the clinical aspects that will be discussed in subsequent volumes in the series
Book Synopsis Fetal-Maternal Immune Interactions in Pregnancy by : Nandor Gabor Than
Download or read book Fetal-Maternal Immune Interactions in Pregnancy written by Nandor Gabor Than and published by Frontiers Media SA. This book was released on 2020-01-24 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Immunology of Pregnancy by : Gil Mor
Download or read book Immunology of Pregnancy written by Gil Mor and published by Springer Science & Business Media. This book was released on 2007-12-27 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers in detail contemporary hypotheses and studies related to the immunology of implantation and provides a practical approach for the application of basic reproductive immunology research to pregnancy complications such as preeclampsia, pre-term labor and IUGR. Provides complete and up to date review of current knowledge of the role of the immune system during pregnancy and the interactions between the placenta and the maternal immune system.
Book Synopsis Immunopharmacology and Inflammation by : Carlo Riccardi
Download or read book Immunopharmacology and Inflammation written by Carlo Riccardi and published by Springer. This book was released on 2018-06-09 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive overview of the current research on inflammation and immunopharmacology, with particular attention to the use of anti-inflammatory drugs, this book discusses future trends in this area of pharmacological research. It addresses an audience with basic knowledge in the inflammatory process, immune system and pharmacology. The book meets the needs of graduate students, junior and senior researchers and is useful as a source of the most current information for those already working in these fields.
Book Synopsis Vascular Biology of the Placenta by : Yuping Wang
Download or read book Vascular Biology of the Placenta written by Yuping Wang and published by Biota Publishing. This book was released on 2017-06-23 with total page 126 pages. Available in PDF, EPUB and Kindle. Book excerpt: The placenta is an organ that connects the developing fetus to the uterine wall, thereby allowing nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. Proper vascular development in the placenta is fundamental to ensuring a healthy fetus and successful pregnancy. This book provides an up-to-date summary and synthesis of knowledge regarding placental vascular biology and discusses the relevance of this vascular bed to the functions of the human placenta.
Book Synopsis Immunology of Pregnancy by : Udo R. Markert
Download or read book Immunology of Pregnancy written by Udo R. Markert and published by Karger Medical and Scientific Publishers. This book was released on 2005-01-01 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents the discipline of immunology which studies a unique physiological phenomenon contradicting many of the generally established rules in the field: immunology of pregnancy. It provides a wide overview of the current research of this topic. Prominent and leading international groups contributed by reviewing the most significant findings in the field.
Book Synopsis The Placenta, Fetomaternal Tolerance and Beyond: A Tribute to Sir Peter Medawar on the 60th Anniversary of his Nobel Prize by : Gabriela Barrientos
Download or read book The Placenta, Fetomaternal Tolerance and Beyond: A Tribute to Sir Peter Medawar on the 60th Anniversary of his Nobel Prize written by Gabriela Barrientos and published by Frontiers Media SA. This book was released on 2022-09-16 with total page 301 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Placental and Gestational Pathology with Online Resource by : Raymond W. Redline
Download or read book Placental and Gestational Pathology with Online Resource written by Raymond W. Redline and published by Cambridge University Press. This book was released on 2018-08-23 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: A guide to identifying disease processes in the placenta affecting pregnancy outcome, with current diagnostic criteria and clinical consequences.
Book Synopsis Immune Regulations in Reproductive Organs and Organ Transplant by : Lei Huang
Download or read book Immune Regulations in Reproductive Organs and Organ Transplant written by Lei Huang and published by Frontiers Media SA. This book was released on 2022-04-18 with total page 388 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Maternal Fetal Interface by : Anthony Carter
Download or read book The Maternal Fetal Interface written by Anthony Carter and published by Boydell & Brewer. This book was released on 1998 with total page 456 pages. Available in PDF, EPUB and Kindle. Book excerpt: The 29 papers contained in this volume look closely at various aspects of what is termed, "The Maternal-Fetal Interface," as it relates to the latest research in placental science. A substantial section of the book is devoted to the troublesome question of vertical transmission of infectious agents: namely, the HIV-1 virus. However, other sections of the volume examine related issues such as drug and toxin transfer across the term placenta and the diversity of placental types and how this can affect a placenta's effectiveness as a barrier. Anthony Carter is at the University of Odense, Denmark Vibeke Dantzer is at the University of Copenhagen, DenmarkThomas Jansson is at the University of Gothenburg, Sweden
Book Synopsis Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis by : Sandra Hellberg
Download or read book Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis written by Sandra Hellberg and published by Linköping University Electronic Press. This book was released on 2019-10-22 with total page 118 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is characterized by a dysregulated immune system leading to chronic inflammation in the central nervous system. Despite increasing number of treatments, many patients continue to deteriorate. A better understanding of the underlying disease mechanisms involved in driving disease is a pre-requisite for finding new biomarkers and new treatment targets. The improvement of MS during pregnancy, comparable to the beneficial effects of the most effective treatment, suggests that the transient and physiological immune tolerance established during pregnancy could serve as a model for successful immune regulation. Most likely the immune-endocrine alterations that take place during pregnancy to accommodate the presence of the semi-allogenic fetus contribute to the observed disease improvement. The aim of this thesis was to characterize the dysregulated immune system in MS and define potential factors and mechanisms established during pregnancy that could be involved in the pregnancy-induced effects in MS, focusing on CD4+ T cells as one of the main drivers in immunity and in the MS pathogenesis. Using a network-based modular approach based on gene expression profiling, we could show that CD4+ T cells from patients with MS displayed an altered dynamic gene response to activation, in line with a dysregulated immune system in MS. The resulting gene module disclosed cell activation and chemotaxis as central components in the deviating response, results that form a basis for further studies on its modulation during pregnancy. Moreover, a combination of secreted proteins (OPN+CXCL1-3+CXCL10-CCL2), identified from the module, could be used to separate patients and controls, predict disease activity after 2 years and discriminate between high and low responders to treatment, highlighting their potential use as biomarkers for predicting disease activity and response to treatment. The pregnancy hormone progesterone (P4), a potential factor involved in the pregnancy-induced amelioration of MS, was found to significantly dampen CD4+ T cell activation. Further detailed transcriptomic profiling revealed that P4 almost exclusively down-regulated immune-related pathways in activated T cells, several related to or downstream of T cell activation such as JAKSTAT signaling, T cell receptor signaling and cytokine-cytokine receptor interaction. In particular, P4 significantly affected genes of relevance to diseases known to be modulated during pregnancy, where genes associated to MS were most significantly affected, supporting a role for P4 in the pregnancy-induced immunomodulation. By using another approach, the role of thymus in T cell regulation during pregnancy was assessed. Two established measures of thymic output, CD31 expression and TREC content, were used and showed that thymic output of T cells is maintained during human pregnancy, or even possibly increased in terms of regulatory T cells. This thesis further supports a pivotal role for CD4+ T cells and T cell activation in the MS pathogenesis and adds to the knowledge of how they could be involved in driving disease. We identified a novel strategy for capturing central aspects of the deviating response to T cell activation that could be translated into potentially clinically relevant biomarkers. Further, P4 is emerging as a promising candidate for the pregnancy-induced immunomodulation that could be of importance as a future treatment option. Lastly, maintained thymic output of T cells during human pregnancy challenges the rodent-based dogma of an inactive thymus during pregnancy. Thymic dysfunction has been reported not only in MS but also in rheumatoid arthritis, another inflammatory disease that improves during pregnancy, which highlights a potential role for thymus in immune regulation that could be involved in the pregnancy-induced amelioration.
Download or read book MRCOG Part One written by Alison Fiander and published by Cambridge University Press. This book was released on 2016-10-13 with total page 557 pages. Available in PDF, EPUB and Kindle. Book excerpt: A fully updated and illustrated handbook providing comprehensive coverage of all curriculum areas covered by the MRCOG Part 1 examination.
Book Synopsis Maternal Hemodynamics by : Christoph Lees
Download or read book Maternal Hemodynamics written by Christoph Lees and published by Cambridge University Press. This book was released on 2018-05-03 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: Discover new concepts in cardiovascular and hemodynamic functionality in feto-maternal medicine, from leading experts in the field.