Immune Regulation in Pregnancy

Bonney, Elizabeth A.

doi:10.1016/j.ogc.2016.07.004

Cited by 71 publications

(45 citation statements)

References 170 publications

(163 reference statements)

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“…Since immunosuppression during pregnancy is largely mediated by regulatory T cells [39–44], we determined whether the depletion of CD71+ erythroid cells had an effect on the ex vivo expansion of regulatory T cells (Figure 5A). Depletion of CD71+ erythroid cells did not significantly alter the number of PTL-derived CD4+ regulatory T cells; yet, an expansion of such cells was observed upon T-cell activation via CD3/CD28 stimulation (Figure 5D).…”

Section: Resultsmentioning

confidence: 99%

CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

Miller

Romero

Unkel

et al. 2018

Journal of Leukocyte Biology

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Neonatal CD71+ erythroid cells are thought to have immunosuppressive functions. Recently, we demonstrated that CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor are reduced to levels similar to those of term neonates; yet, their functional properties are unknown. Herein, we investigated the functionality of CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm or term labor. CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor displayed a similar mRNA profile to that of those from term neonates. The direct contact between preterm or term neonatal CD71+ erythroid cells and maternal mononuclear immune cells, but not soluble products from these cells, induced the release of pro-inflammatory cytokines and a reduction in the release of TGFβ. Moreover, PTL-derived neonatal CD71+ erythroid cells: 1) modestly altered CD8+ T cell activation; 2) inhibited conventional CD4+ and CD8+ T-cell expansion; 3) suppressed the expansion of CD8+ regulatory T cells,; 4) regulated cytokine responses mounted by myeloid cells in the presence of a microbial product; and 5) indirectly modulated T-cell cytokine responses. In conclusion, neonatal CD71+ erythroid cells regulate neonatal T-cell and myeloid responses and their direct contact with maternal mononuclear cells induces a pro-inflammatory response. These findings provide insight into the biology of neonatal CD71+ erythroid cells during the physiologic and pathologic processes of labor.

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Section: Resultsmentioning

confidence: 99%

CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

Miller

Romero

Unkel

et al. 2018

Journal of Leukocyte Biology

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“…syphilis [15–19]). Another major immunological function is the successful establishment and maintenance of maternal-fetal tolerance [72, 75, 83, 84, 92, 94, 99, 104, 111], the breakdown of which may lead to maternal antifetal rejection. The clinical spectrum of maternal antifetal rejection may include subclinical semi-allograft rejection detected only at the time of examination of the placenta (by identification of chronic chorioamnionitis [118–122, 124, 126, 128, 129], VUE [122, 123, 126, 130, 131], or chronic deciduitis [122, 126, 129]), preterm labor with intact membranes [118–120, 122, 124–126], PPROM [118], maternal perivillous fibrin deposition [127], and other obstetrical syndromes [121, 122, 126].…”

Section: Discussionmentioning

confidence: 99%

“…Tolerance, “the active state of antigen-specific nonresponsiveness,” leading to diminished reactivity to paternal antigens expressed by the placenta and/or fetus, is considered key for a successful pregnancy [75–78, 83–86, 89–104]. The mechanisms responsible for tolerance in pregnancy have been reviewed by Elizabeth Bonney [90, 91, 93, 104–106], Sing-Sing Way [107, 108], and Adrian Erlebacher [72, 86, 109–112].…”

Section: Introductionmentioning

confidence: 99%

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Fetal death: an extreme manifestation of maternal anti-fetal rejection

Lannaman

Romero

Chaiworapongsa

et al. 2017

Journal of Perinatal Medicine

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Objective The aim of this study was to determine the association between chronic placental inflammation and amniotic fluid (AF) markers of maternal anti-fetal rejection as well as the presence of microorganisms in the AF fluid of patients with fetal death. Study Design This cohort study included 40 patients with fetal death whose placentas were examined for chronic inflammatory lesions and whose AF chemokine ligand (CXCL)10 and interleukin (IL)-6 concentrations were determined by immunoassays. AF was processed for bacteria, mycoplasmas and viruses using cultivation and molecular microbiologic techniques (i.e. PCR-ESI/MS). Results (1) The most prevalent placental findings were maternal vascular underperfusion (63.2%, 24/38), followed by chronic inflammatory lesions (57.9%, 22/38); (2) chronic chorioamnionitis (18/38) was three times more frequent than villitis of unknown etiology (6/38); (3) an elevated AF CXCL10 concentration (above the 95th centile) was present in 60% of the cases, and a receiver operating characteristics (ROC)-derived cut-off of 2.9 ng/mL had a sensitivity of 73% and a specificity of 75% in the identification of chronic placental inflammatory lesions; (4) only five cases had microbial invasion of the amniotic cavity, and the presence of microorganisms did not correlate with chronic placental inflammation. Conclusion In women with unexplained fetal death, there is an association between elevated AF CXCL10 and chronic placental inflammatory lesions. Therefore, we conclude that a subset of patients with fetal death may have endured a breakdown of maternal-fetal tolerance, which cannot be attributed to microorganisms in the amniotic cavity.

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“…This section summarizes key immune players involved in immuno-modulatory events that support normal pregnancy, both the genetic and environmental aspects will be discussed in successive paragraphs. The maternal immune regulation in pregnancy has been extensively described (51) and is beyond the scope of this review.…”

Section: Maternal Immune Response In Pregnancymentioning

confidence: 99%

The Interplay Between Reproductive Tract Microbiota and Immunological System in Human Reproduction

et al. 2020

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In the last decade, the microbiota, i.e., combined populations of microorganisms living inside and on the surface of the human body, has increasingly attracted attention of researchers in the medical field. Indeed, since the completion of the Human Microbiome Project, insight and interest in the role of microbiota in health and disease, also through study of its combined genomes, the microbiome, has been steadily expanding. One less explored field of microbiome research has been the female reproductive tract. Research mainly from the past decade suggests that microbial communities residing in the reproductive tract represent a large proportion of the female microbial network and appear to be involved in reproductive failure and pregnancy complications. Microbiome research is facing technological and methodological challenges, as detection techniques and analysis methods are far from being standardized. A further hurdle is understanding the complex host-microbiota interaction and the confounding effect of a multitude of constitutional and environmental factors. A key regulator of this interaction is the maternal immune system that, during the peri-conceptional stage and even more so during pregnancy, undergoes considerable modulation. This review aims to summarize the current literature on reproductive tract microbiota describing the composition of microbiota in different anatomical locations (vagina, cervix, endometrium, and placenta). We also discuss putative mechanisms of interaction between such microbial communities and various aspects of the immune system, with a focus on the characteristic immunological changes during normal pregnancy. Furthermore, we discuss how abnormal microbiota composition, "dysbiosis," is linked to a spectrum of clinical disorders related to the female reproductive system and how the maternal immune system is involved. Finally, based on the data presented in this review, the future perspectives in diagnostic approaches, research directions and therapeutic opportunities are explored.

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Immune Regulation in Pregnancy

Cited by 71 publications

References 170 publications

CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

Fetal death: an extreme manifestation of maternal anti-fetal rejection

The Interplay Between Reproductive Tract Microbiota and Immunological System in Human Reproduction

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