Placental Ischemia‐Induced TH17 Cells Mediate the Pathophysiology Associated with Preeclampsia

Abstract

Preeclampsia (PE) is associated with hypertension, inflammation, intrauterine growth restriction (IUGR), increased CD4+ THelper 17 cells (TH17s) and agonistic auto‐antibodies to the AT1 receptor (AT1‐AA). The objective of this study was to determine a role for TH17s in mediating pathophysiology associated with PE using the reduced uterine perfusion pressure (RUPP) rat model of PE. On gestation day 12 (GD12) RUPP‐induced TH17s were injected into normal pregnant (NP) rats; On GD19 blood pressure (MAP) was recorded, and blood and tissues were collected. One‐way ANOVA was used for statistical analysis. MAP increased from 99±2 in NP (n=8) to 128±4 in RUPP (n=9) and to 111±3 mmHg in NP+TH17 (n=11; p<0.05). Placental and renal ROS increased from 238 and 411 RLU, respectively, in NP to 328 and 603 RLU in RUPP and to 339 and 833 RLU in NP+TH17 (p<0.05). Importantly pup weight (gm) decreased significantly from 2.19 in NP to 1.91 in RUPP, and to 1.9 in NP+TH17 (p<0.05). Adoptive transfer of TH17s also increased inflammation: IL‐6 increased significantly from 27.5 pg/mL in NP to 62.2 pg/mL in RUPP and to 75.9 pg/mL in NP+TH17 (p<0.5); IL‐17 increased from 0.5 pg/mL in NP to 1.29 pg/mL in RUPP and increased to 5.5 pg/mL in NP+TH17 (p>0.05). AT1‐AA significantly increased from 0.1beats/min in NP to 16.82beats/min in RUPP and to 15.6beats/min in NP+TH17. TH17s induced hypertension, ROS, IUGR, inflammation, and AT1‐AA in pregnant rats, demonstrating the importance of TH17s to mediate the pathophysiology associated with PE and their potential as a new therapeutic target for treatment of PE.NIH grants RO1HD067541 and T32HL105324