Article

Uterine NK cells: active regulators at the maternal-fetal interface

The Journal of clinical investigation (Impact Factor: 13.77). 05/2014; 124(5):1872-1879. DOI: 10.1172/JCI68107
Source: PubMed

ABSTRACT Pregnancy presents an immunological conundrum because two genetically different individuals coexist. The maternal lymphocytes at the uterine maternal-fetal interface that can recognize mismatched placental cells are T cells and abundant distinctive uterine NK (uNK) cells. Multiple mechanisms exist that avoid damaging T cell responses to the fetus, whereas activation of uNK cells is probably physiological. Indeed, genetic epidemiological data suggest that the variability of NK cell receptors and their MHC ligands define pregnancy success; however, exactly how uNK cells function in normal and pathological pregnancy is still unclear, and any therapies aimed at suppressing NK cells must be viewed with caution. Allorecognition of fetal placental cells by uNK cells is emerging as the key maternal-fetal immune mechanism that regulates placentation.

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Available from: Francesco Colucci, Dec 11, 2014
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    • "23 [18–37] ns Systolic blood pressure (mmHg) 12 [10] [11] [12] [13] 14 [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] 12 [10] [11] [12] [13] í µí±ƒ < 0.001 * Diastolic blood pressure (mmHg) 7 [5–8.3] 8.7 [6] [7] [8] [9] [10] [11] [12] 7 [5.5–8.5] í µí±ƒ < 0.001 * Uterine height (cm) 32 [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] 26 [15–36] 26 [15–36] í µí±ƒ < 0.001 § Term at sampling (weeks of gestation) 31.7 [15.3–41] 30 [17–41] 30 [17–41] ns Term at delivery (weeks of gestation) 40.3 [35] [36] [37] [38] [39] [40] [41] [42] 32.3 [17–41.1] "
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    ABSTRACT: Up to 5% of couples at reproductive age suffer from at least two consecutive miscarriages, and around 1% experience three or more consecutive gestational losses, most of them during the first ten weeks of pregnancy, resulting in a significant personal, social and economic public health burden. The pregnancy losses occurring after the twentieth gestational week, namely foetal death or stillbirth, are even more emotionally and psychologically devastating for the couple. In almost half of these cases there is not any known cause of foetal death. In the last years, significant progress in the identification and treatment of the risk factors associated to foetal death has been made: advanced maternal age, obesity, pre-existing maternal diseases or acquired infections during pregnancy; and associated immunological disorders. Among the latter, the most common cause is the obstetric antiphospholipid syndrome, autoimmune disease that can present with placental infarction, thrombosis in the utero-placental circulation and foetal loss. Here we review the evidence of other immunological disorders that have been associated with intrauterine foetal death: non-diagnosed celiac disease, peripheral expansion of natural killer cells and diverse autoimmune or inflammatory abnormalities. The detection and control of such abnormalities in women with history of prior foetal death may lead to a successful subsequent pregnancy.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Up to 5% of couples at reproductive age suffer from at least two consecutive miscarriages, and around 1% experience three or more consecutive gestational losses, most of them during the first ten weeks of pregnancy, resulting in a significant personal, social and economic public health burden. The pregnancy losses occurring after the twentieth gestational week, namely foetal death or stillbirth, are even more emotionally and psychologically devastating for the couple. In almost half of these cases there is not any known cause of foetal death. In the last years, significant progress in the identification and treatment of the risk factors associated to foetal death has been made: advanced maternal age, obesity, pre-existing maternal diseases or acquired infections during pregnancy; and associated immunological disorders. Among the latter, the most common cause is the obstetric antiphospholipid syndrome, autoimmune disease that can present with placental infarction, thrombosis in the utero-placental circulation and foetal loss. Here we review the evidence of other immunological disorders that have been associated with intrauterine foetal death: non-diagnosed celiac disease, peripheral expansion of natural killer cells and diverse autoimmune or inflammatory abnormalities. The detection and control of such abnormalities in women with history of prior foetal death may lead to a successful subsequent pregnancy.
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