The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy, involves imbalanced T helper (TH) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in PreE in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of PreE in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human PreE. AVP infusion throughout gestation in mice resulted in increased pro-inflammatory interferon γ (IFNg) (TH1) in the maternal plasma. The TH17-associated cytokine interleukin (IL)-17 was elevated in the maternal plasma, amniotic fluid, and placenta following AVP infusion. Conversely, the TH2-associated anti-inflammatory cytokine IL-4 was decreased in the maternal and fetal kidneys from AVP-infused dams, while IL-10 was decreased in the maternal kidney and all fetal tissues. Collectively, these results demonstrate the sufficiency of AVP to induce the immune changes typical of PreE. We investigated if T cells can respond directly to AVP by evaluating the expression of AVP receptors (AVPRs) on mouse and human CD4+ T cells. Mouse and human T cells expressed AVPR1a, AVPR1b, and AVPR2. The expression of AVPR1a was decreased in CD4+ T cells obtained from PreE-affected women. In total, our data are consistent with a potential initiating role for AVP in the immune dysfunction typical of PreE and identifies putative signaling mechanism(s) for future investigation.
Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia
Sabrina M. Scroggins, Donna A. Santillan, Jenna M. Lund, Jeremy A. Sandgren, Lindsay K. Krotz, Wendy S. Hamilton, Eric J. Devor, Heather A. Davis, Gary L. Pierce, Katherine N. Gibson-Corley, Curt D. Sigmund, Justin L. Grobe, Mark K. Santillan; Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia. Clin Sci (Lond) 14 February 2018; 132 (3): 419–436. doi: https://doi.org/10.1042/CS20171059
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