Abstract
Despite much interest in the mechanisms regulating fetal-maternal interactions, information on leukocyte populations and major cytokines present in uterus and placenta remains fragmentary. This report presents a detailed and quantitative study of leukocyte populations at the mouse fetal-maternal interface, including a comparison between pregnancies from syngeneic and allogeneic crosses. Our results provide evidence for drastic differences not only in the composition of leukocyte populations in the uterus during pregnancy, but also between uterine and placental tissues. Interestingly, we have observed a significant decrease in the number of myeloid Gr1+ cells including monocytes, and myeloid CD11c+ cells including DCs in placenta from an allogeneic pregnancy. In addition, we have compared the expression levels of a panel of cytokines in non-pregnant (NP) or pregnant mouse uterus, in placenta, or in their isolated resident leukocytes. Qualitative and quantitative differences have emerged between NP, pregnant uterus and placenta. Unexpectedly, IL-9 was the major cytokine in NP uterus, and was maintained at high levels during pregnancy both in uterus and placenta. Moreover, we have found that pregnancy is associated with an increase in uterine IL-1a and a significant decrease in uterine G-CSF and GM-CSF. Comparing allogeneic versus syngeneic pregnancy, less allogeneic placental pro-inflammatory cytokines CCL2 (MCP-1), CXCL10 (IP-10) and more IL1-α in whole uterus was reproducibly observed. To our knowledge, this is the first report showing a detailed overview of the leukocyte and cytokine repertoire in the uterus of virgin females and at the fetal-maternal interface, including a comparison between syngeneic and allogeneic pregnancy. This is also the first evidence for the presence of IL-9 in NP uterus and at the maternal-fetal interface, suggesting a major role in the regulation of local inflammatory or immune responses potentially detrimental to the conceptus.
Highlights
Understanding the intricate mechanisms regulating mammalian fetal-maternal interactions has remained a challenging goal for biologists for several decades [1]
Few studies have described in detail the different leukocyte populations at the fetal-maternal interface, in part due to the difficulty to prepare significant numbers of viable immune cells from the placenta and uterus
Our results have shown that the leukocyte preparations we performed on day 16.5 pc were more than 95% positive for the pan leukocyte marker CD45
Summary
Understanding the intricate mechanisms regulating mammalian fetal-maternal interactions has remained a challenging goal for biologists for several decades [1]. TGFb is a pleiotropic cytokine with potent immunosuppressive activity on the majority of the cellular components of immune responses Both IL-10 and TGFb have been shown to be present in important amounts at the fetal-maternal interface in mice and humans [6,19,20,21,22,23,24], where they are assumed to play an immunoregulatory role. IL-10 was present in large amounts, but surprisingly, out of the panel of cytokines tested, IL-9 was present in largest quantities, in NP and pregnant uterus and placenta To our knowledge, this is the first report demonstrating the presence of important amounts of IL-9 at the fetal-maternal interface. These novel findings are discussed in the light of recent findings on the role of IL-9 in the induction of immunological tolerance to allografts
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