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Progesterone Modulation of Pregnancy-Related Immune Responses

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Title: Progesterone Modulation of Pregnancy-Related Immune Responses
Authors: Shah, NM
Imami, N
Johnson, MR
Item Type: Journal Article
Abstract: Progesterone (P4) is an important steroid hormone for the establishment and maintenance of pregnancy and its functional withdrawal in reproductive tissue is linked with the onset of parturition. However, the effects of P4 on adaptive immune responses are poorly understood. In this study, we took a novel approach by comparing the effects of P4 supplementation longitudinally, with treatment using a P4 antagonist mifepristone (RU486) in mid-trimester pregnancies. Thus, we were able to demonstrate the immune-modulatory functions of P4. We show that, in pregnancy, the immune system is increasingly activated (CD38, CCR6) with greater antigen-specific cytotoxic T cell responses (granzyme B). Simultaneously, pregnancy promotes a tolerant immune environment (IL-10 and regulatory-T cells) that gradually reverses prior to the onset of labor. P4 suppresses and RU486 enhances antigen-specific CD4 and CD8 T cell inflammatory cytokine (IFN-γ) and cytotoxic molecule release (granzyme B). P4 and RU486 effectively modulate immune cell-mediated interactions, by regulating differentiated memory T cell subset sensitivity to antigen stimulation. Our results indicate that P4 and RU486, as immune modulators, share a reciprocal relationship. These data unveil key contributions of P4 to the modulation of the maternal immune system and suggests targets for future modulation of maternal immune function during pregnancy.
Issue Date: 20-Jun-2018
Date of Acceptance: 23-May-2018
URI: http://hdl.handle.net/10044/1/60736
DOI: https://dx.doi.org/10.3389/fimmu.2018.01293
ISSN: 1664-3224
Publisher: FRONTIERS MEDIA SA
Journal / Book Title: FRONTIERS IN IMMUNOLOGY
Volume: 9
Copyright Statement: © 2018 Shah, Imami and Johnson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Imperial College Trust
Funder's Grant Number: Mark Johnson's IC Trust Acct
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
pregnancy
progesterone
RU486
immune modulation
immune response
REGULATORY T-CELLS
BLOOD MONONUCLEAR-CELLS
BLOCKING FACTOR PIBF
NATURAL-KILLER-CELL
MENSTRUAL-CYCLE
GLUCOCORTICOID-RECEPTOR
PERIPHERAL-BLOOD
ANTIRETROVIRAL THERAPY
SPONTANEOUS-ABORTION
ADOPTIVE TRANSFER
Publication Status: Published
Article Number: ARTN 1293
Online Publication Date: 2018-06-20
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



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