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Molecular mechanisms of hormonal and hormonal-cytokine control of immune tolerance in pregnancy

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

The molecular mechanisms of immunomodulatory effects of the major reproductive hormones (human chorionic gonadotropin, leptin, ghrelin, progesterone, estriol, estradiol) underlying the formation of maternal tolerance to semiallogeneic fetus in different trimesters of human pregnancy are reviewed. New data on the effect of hormonal ensembles and hormonal-cytokine combinations, which are most significant for the formation of immune tolerance during physiological pregnancy, are presented. Possible pathways of hormonal and hormonal-cytokine signal transduction driving the induction of adaptive regulatory T cells and the expression of indoleamine 2,3-dioxygenase in monocytes as a basis of immune tolerance are analyzed.

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Abbreviations

LPS:

lipopolysaccharide

PBMC:

peripheral blood mononuclear cells

hCG:

human chorionic gonadotropin

CTL:

cytotoxic T lymphocyte

AC:

adenylyl cyclase

AP-1:

activating protein 1

APC:

antigen-presenting cell

cAMP:

adenosine-3′,5′-cyclophosphate

CBP:

CREB-binding protein

CD:

the cluster of differentiation

CNS:

conserved noncoding sequence

CRE:

cAMP response element

CREB:

the protein binding the cAMP response element

CTLA-4:

cytotoxic T lymphocyte-associated antigen 4

DAG:

diacylglycerol

DC:

dendritic cell

E2 :

estradiol

E3 :

estriol

ER:

estradiol receptor

ERK:

extracellular signal-regulated kinase

FOS:

AP-1 transcription factor component

FOXP3:

forkhead box P3 transcription factor

GAS:

γ-interferon activating sites

GHS-R:

ghrelin receptor

GPCR:

G-protein coupled receptor

GPER1:

G-protein coupled estrogen receptor 1

HePTP:

inhibitory hematopoietic protein tyrosine phosphatase

IDO:

indoleamine 2,3-dioxygenase

IFN:

interferon

IKK:

IκB kinase

IL:

interleukin

IL-2R:

IL-2 receptor

IP3 :

inositol-1,4,5-trisphosphate

JAK:

Janus kinase

JNK:

c-Jun NH2-terminal protein kinase

JUN:

the AP-1 transcription factor component

LEPRb:

leptin receptor

MAPK:

mitogen activated protein kinase

mPR:

membrane P4 receptor

mTOR:

mammalian target of rapamycin

MyD88:

myeloid differentiation primary response protein 88

NF-κB:

nuclear factor κB

NFAT:

nuclear factor of activated Tcells

NK:

natural killer cell

P4 :

progesterone

PDE:

phosphodiesterase

PI3K:

phosphatidylinositol-3 kinase

PIAS3:

protein inhibitor of activated STAT3

PIP2 :

phosphatidylinositol-4,5-disphosphate

PIP3 :

phosphatidylinositol-3,4,5-trisphosphate

PKA:

protein kinase A

PKB/Akt:

protein kinase B

PKC:

protein kinase C

PLC:

phospholipase C

SHP:

tyrosine phosphatase

SOCS3:

suppressor of cytokine signaling 3

STAT:

signal transducer and activator of transcription

TAK:

TGF-β activated kinase

TCR:

T cell receptor

TGF-β:

transforming growth factor β

Th:

helper T lymphocyte

TLR:

Toll-like receptor

TNF-α:

tumor necrosis factor α

TRAIL:

TNF-related apoptosis-inducing ligand

Treg:

regulatory T cell

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  1. Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, ul. Goleva, 13, Perm, 614081, Russia

    S. V. Shirshev

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Original Russian Text © S.V. Shirshev, 2014, published in Biologicheskie Membrany, 2014, Vol. 31, No. 5, pp. 303–322.

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Shirshev, S.V. Molecular mechanisms of hormonal and hormonal-cytokine control of immune tolerance in pregnancy. Biochem. Moscow Suppl. Ser. A 9, 21–39 (2015). https://doi.org/10.1134/S1990747814050079

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