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

doi:10.1042/CS20171059

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Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia

Journal article

Peer reviewed

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, …

Clinical science (1979), Vol.132(3), pp.419-436

02/14/2018

DOI: 10.1042/CS20171059

PMCID: PMC5947858

PMID: 29371289

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Abstract

The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy, involves imbalanced T helper (T ) 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) (T 1) in the maternal plasma. The T 17-associated cytokine interleukin (IL)-17 was elevated in the maternal plasma, amniotic fluid, and placenta following AVP infusion. Conversely, the T 2-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.

Pregnancy

Pre-Eclampsia - chemically induced

Humans

Mice, Inbred C57BL

Male

Vasopressins - metabolism

Arginine Vasopressin - pharmacology

Protein Precursors - metabolism

Placenta - drug effects

Placenta - metabolism

Neurophysins - metabolism

Animals

Arginine Vasopressin - metabolism

T-Lymphocytes - cytology

T-Lymphocytes - drug effects

Female

Pre-Eclampsia - metabolism

Details

Title: Subtitle: Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia
Creators: Sabrina M Scroggins - Center for Immunology and Immune Based Diseases, University of Iowa, Iowa City, IA 52242, U.S.A
Donna A Santillan - Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, U.S.A
Jenna M Lund - Carver College of Medicine, University of Iowa, Iowa City, IA 52242, U.S.A
Jeremy A Sandgren - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, U.S.A
Lindsay K Krotz - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A
Wendy S Hamilton - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A
Eric J Devor - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A
Heather A Davis - University of Iowa
Gary L Pierce - Department of Health and Human Physiology, University of Iowa, Iowa City, IA 52242, U.S.A
Katherine N Gibson-Corley - Department of Pathology, University of Iowa, Iowa City, IA 52242, U.S.A
Curt D Sigmund - Department of Pharmacology, University of Iowa, Iowa City, IA 52242, U.S.A
Justin L Grobe - Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, U.S.A
Mark K Santillan - Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, U.S.A
Resource Type: Journal article
Publication Details: Clinical science (1979), Vol.132(3), pp.419-436
DOI: 10.1042/CS20171059
PMID: 29371289
PMCID: PMC5947858
NLM abbreviation: Clin Sci (Lond)
ISSN: 0143-5221
eISSN: 1470-8736
Publisher: England
Grant note: R00 HL098276 / NHLBI NIH HHS L30 HD070302 / NICHD NIH HHS U54 TR001356 / NCATS NIH HHS T32 AI007260 / NIAID NIH HHS K12 HD000849 / NICHD NIH HHS T32 GM007337 / NIGMS NIH HHS P01 HL084207 / NHLBI NIH HHS R01 HL134850 / NHLBI NIH HHS KL2 RR024980 / NCRR NIH HHS K99 HL098276 / NHLBI NIH HHS
Language: English
Date published: 02/14/2018
Academic Unit: Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Obstetrics and Gynecology; Neuroscience and Pharmacology; Health, Sport, and Human Physiology ; Ophthalmology and Visual Sciences
Record Identifier: 9983930207002771

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