Lessons from Reproductive Immunology for Other Fields of Immunology and Clinical Approaches

Markert, Udo R.; Fitzgerald, Justine S.; Seyfarth, Lydia; Heinzelmann, Joana; Varosi, Frauke; Voigt, Sandra; Schleußner, E; Seewald, Hans-Joachim

doi:10.1159/000087965

Cited by 9 publications

(7 citation statements)

References 55 publications

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“…During PE, reduced levels of IL-10 have been observed in circulation and in the placenta (143, 146, 147). Previous studies have demonstrated IL-10 to be a potent cytokine that regulates vasculature function and prevents vascular dysfunction (131, 146).…”

Section: The Effect Of Decreased Tregs and Il-10 In Preeclampsiamentioning

confidence: 99%

The role of inflammation in the pathology of preeclampsia

et al. 2016

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Preeclampsia (PE) affects 5–7% of all pregnancies in the U.S. and is the leading cause of maternal and prenatal morbidity. PE is associated with hypertension after week 20 of gestation, decreased renal function, and small-for-gestational-age babies. Women with PE exhibit chronic inflammation and production of autoantibodies. It is hypothesized that during PE, placental ischemia occurs as a result of shallow trophoblast invasion which is associated with an immune imbalance where pro-inflammatory CD4+ T cells are increased and T regulatory cells (Tregs) are decreased. This imbalance leads to chronic inflammation characterized by oxidative stress, pro-inflammatory cytokines, and autoantibodies. Studies conducted in our laboratory have demonstrated the importance of this immune imbalance to cause hypertension in response to placental ischemia in pregnant rats. These studies confirm that increased CD4+ T cells and decreased Tregs during pregnancy leads to elevated inflammatory cytokines, endothelin (ET-1), reactive oxygen species (ROS), and agonistic autoantibodies to the Angiotensin II (Ang II), type 1 receptor (AT1-AA). All of these factors taken together play an important role in increasing the blood pressure during pregnancy. Specifically, this review focuses on the decrease in Tregs, and their associated regulatory cytokine IL-10, which is seen in response to placental ischemia during pregnancy. This study will also examine the effect of regulatory immune cell repopulation on the pathophysiology of preeclampsia. These studies show that restoring the balance of the immune system through increasing Tregs, either by adoptive transfer or by infusing IL-10, reduces the blood pressure and pathophysiology associated with placental ischemia in pregnant rats.

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Section: The Effect Of Decreased Tregs and Il-10 In Preeclampsiamentioning

confidence: 99%

The role of inflammation in the pathology of preeclampsia

et al. 2016

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“…A voluminous research literature now indicates that pregnancy introduces broad and marked modulation of both innate and adaptive immune function (20)(21)(22)(23)(24). Interest in those immune alterations stemmed from the recognition that they are key factors in understanding how the semiallogeneic embryo escapes from rejection.…”

Section: Immunomodulation Associated With Pregnancymentioning

confidence: 99%

“…25,29,80,81), but also the release of various immunomodulatory molecules that have a systemic effect. MICA/B, s-HLA-G, IL-6, IL-10, transforming growth factor-h, and progesterone-induced blocking factor are often found at increased level in the circulation of both cancer patients and pregnant women and are thought to assist the tumor and the fetus to escape attack by the immune system (20,27,80,82).…”

Section: Does the Effect Of Pregnancy On Immune Functionmentioning

confidence: 99%

Heightened Risk of Breast Cancer Following Pregnancy: Could Lasting Systemic Immune Alterations Contribute?

Shakhar

Valdimarsdottir

Bovbjerg

2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The protective effect of having a first full-term pregnancy (FFTP) at a younger age on women's lifetime risk of breast cancer is well known. Less appreciated is the increased risk seen in the years immediately following pregnancy. This adverse effect is more pronounced and more prolonged in women with later age at FFTP. The mechanisms responsible for this increased risk are still poorly understood. In the present paper, we put forward the hypothesis that the marked peripheral immune changes induced by pregnancy may account for these effects. We highlight immune changes that characterize the unique immune state of pregnancy (a combination of cellular immunosuppression and enhanced inflammatory response), note the resemblance of these changes to cancer escape mechanisms, and discuss why such immune changes may be critical for the development of breast cancer following pregnancy. We further support this idea by initial findings from our own laboratory that the age at FFTP is negatively related to natural killer cell cytotoxicity many years later and propose possible models for the kinetics of the immune changes during and following pregnancy. The effect of age at FFTP on the immune function is currently understudied. Its potential relevance to the development of breast cancer stresses the need for further research. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1082 -6) The widely known protective effect of having a first full-term pregnancy (FFTP) at an earlier age on women's lifetime risk of developing breast cancer has been extensively documented over the past 30 years and is included as a factor in the classic Gail model of breast cancer risk (1). Less widely appreciated are more recent data from large-scale studies indicating that this protective effect is preceded by a period of increased risk for breast cancer, especially among women with later age at FFTP (2-8). This increased risk of developing breast cancer is both more pronounced and more prolonged in women with later age at FFTP (3)(4)(5)8). Indeed, the crossover from increased to decreased risk of breast cancer following pregnancy, which occurs after about 10 years for women whose FFTP was before the age of 25, occurs only after about 20 years for women whose FFTP was between 25 and 29, and may never crossover for women whose FFTP occurred after the age of 35 (3, 10).The mechanisms underlying what has been termed the ''dual'' effect of pregnancy on breast cancer risk are largely unknown. Reduced susceptibility to carcinogenesis due to terminal differentiation of mammary gland stem cells is increasingly recognized as a likely mechanism for the longterm reduction of risk following an early pregnancy (2,11,12). To date, speculation concerning the mechanisms responsible for the initial increased risk of breast cancer following pregnancy has also centered on possible effects on breast tissues, including the extracellular matrix (2, 13). These effects are most commonly attributed to the high proliferative rate of breast cells during pregnancy and t...

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“…Further investigations in transplant immunology under gender-specific view are currently under way. [15][16][17] Conclusions Female donor hearts lead to a higher early mortality in male recipients and male donor hearts lead to better short-term results in female recipients. In long-term, corrected for early mortality, female donor hearts are superior-specifically in female recipients.…”

Section: Discussionmentioning

confidence: 97%