Increased maternal T cell microchimerism in the allogeneic fetus during LPS-induced preterm labor in mice

Wegorzewska, Marta; Le, Tom; Tang, Qizhi; MacKenzie, Tippi C.

doi:10.1080/19381956.2014.1002703

Cited by 17 publications

(12 citation statements)

References 33 publications

(37 reference statements)

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“…Therefore, in this context, maternal microchimerism is a critical element in promoting maternal-fetal tolerance at baseline. There is evidence that the amount of naturally occurring maternal microchimerism can increase during pregnancy complications (22, 44). We therefore examined whether there are changes in maternal microchimerism in the fetal circulation during PTL by identifying nonshared alleles [human leukocyte antigen–DR (HLA-DR) and In-Del] between the mother and the fetus and using quantitative reverse transcription polymerase chain reaction (RT-PCR) to amplify nonshared maternal alleles in fetal blood or nonshared fetal alleles in maternal blood (45, 46).…”

Section: Resultsmentioning

confidence: 99%

Alloreactive fetal T cells promote uterine contractility in preterm labor via IFN-γ and TNF-α

et al. 2018

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Healthy pregnancy is the most successful form of graft tolerance, whereas preterm labor (PTL) may represent a breakdown in maternal-fetal tolerance. Although maternal immune responses have been implicated in pregnancy complications, fetal immune responses against maternal antigens are often not considered. To examine the fetal immune system in the relevant clinical setting, we analyzed maternal and cord blood in patients with PTL and healthy term controls. We report here that the cord blood of preterm infants has higher amounts of inflammatory cytokines and a greater activation of dendritic cells. Moreover, preterm cord blood is characterized by the presence of a population of central memory cells with a type 1 T helper phenotype, which is absent in term infants, and an increase in maternal microchimerism. T cells from preterm infants mount a robust proliferative, proinflammatory response to maternal antigens compared to term infants yet fail to respond to third-party antigens. Furthermore, we show that T cells from preterm infants stimulate uterine myometrial contractility through interferon-γ and tumor necrosis factor-α. In parallel, we found that adoptive transfer of activated T cells directly into mouse fetuses resulted in pregnancy loss. Our findings indicate that fetal inflammation and rejection of maternal antigens can contribute to the signaling cascade that promotes uterine contractility and that aberrant fetal immune responses should be considered in the pathogenesis of PTL.

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Section: Resultsmentioning

confidence: 99%

Alloreactive fetal T cells promote uterine contractility in preterm labor via IFN-γ and TNF-α

et al. 2018

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“…As detectable amounts of MMC cells are transferred across the placenta to the fetus during pregnancy, there is a possibility for these cells to play a role in initiating the timing of birth. Indeed, increased MMC with T or B cells or myeloid cell phenotypes were found in mouse fetuses from mothers mated allogeneically and treated with LPS in late gestation [69]. In a human study, increased fetal DC and T cell activation in cord blood of preterm infants was associated with an increase in MMCs compared with term cord blood.…”

Section: The Potential Role Of Fmc and MMC In Ptbmentioning

confidence: 95%

Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus

2020

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Preterm birth (PTB) complicates 5–18% of pregnancies globally and is a leading cause of maternal and fetal morbidity and mortality. Most PTB is spontaneous and idiopathic, with largely undefined causes. To increase understanding of PTB, much research in recent years has focused on using animal models to recapitulate the pathophysiology of PTB. Dysfunctions of maternal immune adaptations have been implicated in a range of pregnancy pathologies, including PTB. A wealth of evidence arising from mouse models as well as human studies is now available to support that PTB results from a breakdown in fetal-maternal tolerance, along with excessive, premature inflammation. In this review, we examine the current knowledge of the bidirectional communication between fetal and maternal systems and its role in the immunopathogenesis of PTB. These recent insights significantly advance our understanding of the pathogenesis of PTB, which is essential to ultimately designing more effective strategies for early prediction and subsequent prevention of PTB.

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“…Pathological inflammation can result from the activation of innate (10-15) or adaptive (16-19) immunity. Among innate immune cells, macrophages play a central role throughout pregnancy (20-26) and seem to participate in the mechanisms implicated in spontaneous preterm labor (27-30).…”

Section: Introductionmentioning

confidence: 99%

An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment

Romero

Miller

et al. 2016

The Journal of Immunology

153

137

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Macrophages are implicated in the local inflammatory response that accompanies spontaneous preterm labor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo an M1 polarization during spontaneous preterm labor and that PPARγ activation via rosiglitazone would attenuate the macrophage-mediated inflammatory response, preventing preterm birth. Herein, we show that: 1) decidual macrophages undergo an M1-like polarization during spontaneous term and preterm labor; 2) M2-like macrophages are more abundant than M1-like macrophages in decidual tissue; 3) decidual M2-like macrophages are reduced in preterm pregnancies compared to term pregnancies, regardless of the presence of labor; 4) decidual macrophages express high levels of TNF and IL12, but low levels of PPARγ, during spontaneous preterm labor; 5) decidual macrophages from women who underwent spontaneous preterm labor display plasticity by M1↔M2 polarization in vitro; 6) incubation with rosiglitazone reduces the expression of TNF and IL12 in decidual macrophages from women who underwent spontaneous preterm labor; and 7) treatment with rosiglitazone reduces the rate of LPS-induced preterm birth and improves neonatal outcomes by reducing the systemic pro-inflammatory response in B6 mice and down-regulating mRNA and protein expression of NFκB, TNF, and IL10 in decidual and myometrial macrophages. In summary, we demonstrated that decidual M1-like macrophages are associated with spontaneous preterm labor, and that PPARγ activation via rosiglitazone can attenuate the macrophage-mediated pro-inflammatory response, preventing preterm birth and improving neonatal outcomes. These findings suggest that the PPARγ pathway is a new molecular target for future preventative strategies for spontaneous preterm labor/birth.

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Increased maternal T cell microchimerism in the allogeneic fetus during LPS-induced preterm labor in mice

Cited by 17 publications

References 33 publications

Alloreactive fetal T cells promote uterine contractility in preterm labor via IFN-γ and TNF-α

Alloreactive fetal T cells promote uterine contractility in preterm labor via IFN-γ and TNF-α

Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus

An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment

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