Dendritic Cells: Key to Fetal Tolerance?1

Blois, Sandra M.; Kämmerer, Ulrike; Soto, Catalina Dirney Alba; Tometten, Mareike; Shaikly, Valerie; Barrientos, Gabriela; Jurd, Richard D.; Rukavina, Daniel; Thomson, Angus W.; Klapp, Burghard F.; Fernández, Nelson; Arck, Petra C.

doi:10.1095/biolreprod.107.060632

Cited by 175 publications

(146 citation statements)

References 98 publications

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“…54 DCs are considered to be the immune 'guardians' in the uterine-mucosa, capable of inducing tolerance under normal physiological conditions. 55 DCs in the decidua produce less IL-12 than do peripheral blood DCs, and decidual myeloid DCs induce a higher percentage of T-helper type 2 (Th2) lymphocytes than do peripheral blood DCs.…”

Section: Recruitment Of Antigen-presenting Cells (Macrophages and Dcs)mentioning

confidence: 99%

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

2014

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Embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.

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Section: Recruitment Of Antigen-presenting Cells (Macrophages and Dcs)mentioning

confidence: 99%

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

2014

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“…The encounter of seminal fluid with maternal DCs present either in vaginal lumen or in endometrial tissue at the time of mating 25 represents therefore the first event leading to a protective adaptive immune response. It has been proved that uterine DCs are rather tolerogenic DCs than mature DCs 26 and Heme Oxygenase-1 (HO-1) seems to be pivotal in maintaining maternal DCs in an immature state, which contributes to the expansion of the peripheral Treg population. 27 Not only does the seminal fluid provide the antigens to be presented to APCs but also recruits Treg into the uterus or drives their expansion and the draining lymph nodes as demonstrated by the lack of expansion of Treg after in females mated with males without seminal vesicles but not with vasectomized males 19 Much attention was focused in the production of cytokines by CD4 T helper cells particularly after Piccinni and colleagues showed that decidual T cells from women with unexplained recurrent abortions produced abnormally low Leukemia inhibtory factor (LIF), IL-4, and IL-10 levels.…”

Section: Tafurimentioning

confidence: 99%

Adaptive Immune Responses During Pregnancy

Zenclussen

2013

American J Rep Immunol

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It has long been believed that there is no immune interaction between mother and conceptus during pregnancy. This concept changed after evidence was provided that the maternal immune system is aware of the semiallogeneic conceptus and develops strategies to tolerate it. Since then, finely regulated mechanisms of active tolerance toward the fetus have been described. This Special Issue of the American Journal of Reproductive Immunology deals with these mechanisms. It begins with the description of minor histocompatibility antigens in the placenta; it further goes through adaptive immune responses toward paternal fetal antigens, mostly concentrating on regulatory T cells and molecules modulating the Th1/Th2 balance. The participation of antibody‐producing B cells in normal and pathological pregnancies is also discussed. This introductory chapter resumes the concepts presented throughout the Issue and discusses the clinical applications raised from these concepts.

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“…in the events underpinning successful embryo implantation and establishment of pregnancy, through their roles in decidual tissue remodeling and angiogenesis, and in the induction of maternal-fetal tolerance (1,2). This has led to a focus on identifying the factors that regulate DCs in the uterine endometrium, since deficiency in these cells is implicated in forms of infertility where the endometrium is not receptive to implanting embryos, or in preeclampsia where immune tolerance of the placenta is insufficient (3)(4)(5).…”

Section: Endritic Cells (Dcs) Have Emerged As a Critical Cell Lineagementioning

confidence: 99%

GM-CSF Is an Essential Regulator of T Cell Activation Competence in Uterine Dendritic Cells during Early Pregnancy in Mice

Moldenhauer

Keenihan

Hayball

et al. 2010

The Journal of Immunology

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Uterine dendritic cells (DCs) are critical for activating the T cell response mediating maternal immune tolerance of the semiallogeneicfetus. GM-CSF (CSF2), a known regulator of DCs, is synthesized by uterine epithelial cells during induction of tolerance in early pregnancy. To investigate the role of GM-CSF in regulating uterine DCs and macrophages, Csf2-null mutant and wild-type mice were evaluated at estrus, and in the periconceptual and peri-implantation periods. Immunohistochemistry showed no effect of GM-CSF deficiency on numbers of uterine CD11c+ cells and F4/80+ macrophages at estrus or on days 0.5 and 3.5 postcoitum, but MHC class II+ and class A scavenger receptor+ cells were fewer. Flow cytometry revealed reduced CD80 and CD86 expression by uterine CD11c+ cells and reduced MHC class II in both CD11c+ and F4/80+ cells from GM-CSF–deficient mice. CD80 and CD86 were induced in Csf2−/− uterine CD11c+ cells by culture with GM-CSF. Substantially reduced ability to activate both CD4+ and CD8+ T cells in vivo was evident after delivery of OVA Ag by mating with Act-mOVA males or transcervical administration of OVA peptides. This study shows that GM-CSF regulates the efficiency with which uterine DCs and macrophages activate T cells, and it is essential for optimal MHC class II- and class I-mediated indirect presentation of reproductive Ags. Insufficient GM-CSF may impair generation of T cell-mediated immune tolerance at the outset of pregnancy and may contribute to the altered DC profile and dysregulated T cell tolerance evident in infertility, miscarriage, and preeclampsia.

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Dendritic Cells: Key to Fetal Tolerance?1

Cited by 175 publications

References 98 publications

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

Adaptive Immune Responses During Pregnancy

GM-CSF Is an Essential Regulator of T Cell Activation Competence in Uterine Dendritic Cells during Early Pregnancy in Mice

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