Activation of IL-17 during pregnancy; a link between autoimmunity and preeclampsia

New onset hypertension with proteinuria during pregnancy, preeclampsia is vastly becoming associated with chronic immune activation. Placental ischemia in preeclampsia leads to a showering of immune factors into the maternal circulation and contributes to the development of hypertension. An imbalance between regulatory and effector T (CD4+ T lymphocytes) occurs in patients with preeclampsia. Recent studies show that preeclampsia is associated with activation of autoimmune cells, TH17, secreting interleukin-17, an inflammatory cytokine strongly associated with autoimmune disease. T helper cells termed IL17-producing CD4(+)T cells or "Th17 cells", the cellular component in autoimmune disease, is associated with preeclampsia but the stimulus for this immune dysregulation and a role for IL17 to increase blood pressure in preeclampsia is unknown.;Furthermore, reactive oxygen species (ROS) specifically placental oxidative stress is thought to be one important pathophysiological mediator of preeclampsia. Also severity of preeclampsia is strongly associated with levels of activating autoantibodies to the angiotensin II type I receptor. The objective of our study was to determine if hypertension in preeclampsia is mediated via IL 17 and chronic exposure to IL-17 during pregnancy increases blood pressure by stimulating oxidative stress and AT1-AAs.;In our study, MAP was increased in RUPP rats. CD4+T cells were found to be increased and so were the circulating IL17 levels in this group of animals. These results are similar to increase in circulating IL17 in preeclamptic pregnant women. After chronic exposure of IL17 during pregnancy, MAP was increased and so were urinary isoprostane and placental ROS. Importantly AT1-AA increased in IL-17 infused rats. These data indicate that chronic IL-17 causes placental oxidative stress which serves as stimulus modulating AT1-AA production which plays an important role in mediating IL-17 induced hypertension during pregnancy.;Pre-treatment with Tempol, a ROS scavenger, attenuated placental ROS production and rise in MAP in response to IL 17 excess. The increased tissue oxidative stress produced by IL 17 infusion may be mediated through NADPH oxidases. These novel findings suggest that ROS are important in mediating hypertension in response to IL17-producing CD4(+)T cells or "Th17 cells", the cellular component in autoimmune disease.