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.
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A representative image of an airway from a mouse sensitized and challenged with an allergen. The histological image was captured 24 hours after allergen exposure at which point airway hyperresponsiveness persists without any discernible change to wall structure. In Clinical Science volume 132, issue 3, Wang et al. report on the effects of airway remodelling and allergy on airway responsiveness; for details see pages 327–338. Image kindly provided by Kimberley C.W. Wang (The University of Western Australia).
Research Article|
February 14 2018
Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia
Sabrina M. Scroggins;
Sabrina M. Scroggins
1Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A.
2Center for Immunology and Immune Based Diseases, University of Iowa, Iowa City, IA 52242, U.S.A.
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Donna A. Santillan;
Donna A. Santillan
1Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A.
2Center for Immunology and Immune Based Diseases, University of Iowa, Iowa City, IA 52242, U.S.A.
3Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, U.S.A.
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Jenna M. Lund;
Jenna M. Lund
4Carver College of Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
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Jeremy A. Sandgren;
Jeremy A. Sandgren
4Carver College of Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
5Department of Pharmacology, University of Iowa, Iowa City, IA 52242, U.S.A.
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Lindsay K. Krotz;
Lindsay K. Krotz
1Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A.
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Wendy S. Hamilton;
Wendy S. Hamilton
1Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A.
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Eric J. Devor;
Eric J. Devor
1Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A.
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Heather A. Davis;
Heather A. Davis
6Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242, U.S.A.
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Gary L. Pierce;
Gary L. Pierce
3Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, U.S.A.
7Department of Health and Human Physiology, University of Iowa, Iowa City, IA 52242, U.S.A.
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Katherine N. Gibson-Corley;
Katherine N. Gibson-Corley
8Department of Pathology, University of Iowa, Iowa City, IA 52242, U.S.A.
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Curt D. Sigmund;
Curt D. Sigmund
3Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, U.S.A.
5Department of Pharmacology, University of Iowa, Iowa City, IA 52242, U.S.A.
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Justin L. Grobe;
3Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, U.S.A.
5Department of Pharmacology, University of Iowa, Iowa City, IA 52242, U.S.A.
9Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, U.S.A.
10Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, U.S.A.
Correspondence: Mark K. Santillan ([email protected]) or Justin L. Grobe ([email protected])
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Mark K. Santillan
1Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, U.S.A.
2Center for Immunology and Immune Based Diseases, University of Iowa, Iowa City, IA 52242, U.S.A.
3Center for Hypertension Research, University of Iowa, Iowa City, IA 52242, U.S.A.
Correspondence: Mark K. Santillan ([email protected]) or Justin L. Grobe ([email protected])
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Publisher: Portland Press Ltd
Received:
October 13 2017
Revision Received:
January 03 2018
Accepted:
January 04 2018
Accepted Manuscript online:
January 25 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (3): 419–436.
Article history
Received:
October 13 2017
Revision Received:
January 03 2018
Accepted:
January 04 2018
Accepted Manuscript online:
January 25 2018
Citation
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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