IL17 administration in the Absence of T cells Results in Hypertension, NK cell Activation, and Reduced Pup Weight at Birth, but No Changes in Blood Pressure or Weight at Maturation of Offspring
Authors: Fitzgerald Sarah , Hogg James , Deer Evangeline , Herrock Owen T. , Lemon Jay' P. , Turner Ty , Ibrahim Tarek , Cockrell Kathy , Campbell Nathan , Cornelius Denise , Lamarca Babbette 
Published: May 2022

Preeclampsia (PE) is characterized by new onset hypertension (HTN), fetal growth restriction (FGR), multi‐organ dysfunction, and increased inflammatory cytokines. Moreover, we have shown offspring of RUPP rats develop hypertension at different stages of life based on sex. More recent studies demonstrate a role for mitochondrial (mt) dysfunction/mtROS in the pathogenesis of the disease, however, causative factors for mt dysfunction are still being identified. Th17 cells stimulated by a rat model of PE have been shown to cause HTN, FGR, and mt dysfunction. One of the main cytokines produced by TH17 cells is IL‐17, which we have shown to cause HTN, mtROS, stimulate TH17 cell proliferation, and activate natural killer (NK) cells in pregnant Sprague Dawley rats. The athymic nude rat model lacks T cells, and therefore are useful in examining the differences in the roles of IL‐17 and TH17 cells in the pathophysiology of PE. We hypothesize that IL‐17 induces HTN and is associated with renal and placental mt dysfunction during pregnancy in the absence of T cells in pregnant athymic nude rats. We further hypothesize that offspring of these animals generate hypertension at maturation (16 weeks of age). IL‐17 (150 pg/day) was infused via osmotic minipumps on gestation day (GD) 14. Blood pressure (MAP) and mt function were measured on GD19 and were compared to normal pregnant (NP) rats. Pups were weaned 3 weeks after birth and weighed once a week for 16 weeks, and MAP was measured at 16 weeks. MAP increased in response to IL‐17 (NP+IL‐17, 115.3±1.5 mmHg in, n=6) compared to NP rats (95.5±3.85 mmHg, n=6, p<0.001). Interestingly, mtROS in the absence of T cells is reduced in both the placenta and kidney (46±6.6%fold change in NP+IL‐17 placental mitochondria; 48.8±2.8%fold change in the kidney mitochondria, n=5) compared to NP mtROS (100±6.6%fold change in NP placental mitochondria; 100±3.7% fold change in the kidney mitochondria, (n=4). ADP production in response to IL‐17 in the absence of T cells in the placenta or the kidney increases (105.5±91 pmol of O2/sec/mg, n=3NP+IL‐17 placental mitochondria, 2016±951.2 pmol of O2/sec/mg, n=4, in NP+IL‐17 kidney mitochondria) compared to NP (15.53±1.6 pmol of O2/sec/mg, n=3 NP placenta, 1196±459.5 pmol of O2/sec/mg, n=4 NP kidney (n=4)). Pup weight at GD19 decreased in response to IL‐17 from 1.46±0.2 g in NP (n=6) to 0.98±0.07g in NP+IL‐17 (n=6) in the absence of T cells (p<0.05). However, there was no change in weight after weaning and into adulthood in either male or female offspring. There was also no change in MAP in NP+IL17 (123± 2.7 mmHg, n=3) male offspring compared to NP offspring (122± 2.6 mmHg, n=4) at 16 weeks. There was also no change in female offspring MAP in response to IL‐17 (121± 12 mmHg, n=2) compared to NP (105 ± 21 mmHg, n=3) in offspring at 16 weeks. These results suggest that IL‐17 induces HTN, and FGR without the presence of T cells, and suggests that T cells induce mt dysfunction in PE. It also shows that IL‐17 may not cause hypertension of the offspring after birth.