Rank-Rankl-Opg Axis in Multiple Sclerosis: The Contribution of Placenta

Women with multiple sclerosis (MS) can safely become pregnant and give birth, with no side effects or impediments. Pregnancy is generally accepted as a period of well-being in which relapses have a softer evolution, particularly in the third trimester. Herein, we hypothesized that the placenta, via...

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Published in:Cells (Basel, Switzerland) Switzerland), 2022-04, Vol.11 (8), p.1357
Main Authors: Passaponti, Sofia, Ermini, Leonardo, Acconci, Giulia, Severi, Filiberto Maria, Romagnoli, Roberta, Cutrupi, Santina, Clerico, Marinella, Guerrera, Gisella, Ietta, Francesca
Format: Article
Language:English
Subjects:
Antibiotics
Astrocytes
autoimmune diseases
CCL20 protein
Cell culture
Chemokines
Disease
Experiments
Female
Fetuses
Gene expression
Helper cells
Humans
Ligands
Lymphocytes T
Multiple sclerosis
Multiple Sclerosis - metabolism
NF-κB protein
Obstetrics
Osteoprotegerin
Osteoprotegerin - metabolism
Physiology
Placenta
Placenta - metabolism
Pregnancy
Protein Binding
Proteins
RANK Ligand - metabolism
Receptor Activator of Nuclear Factor-kappa B - metabolism
Secretome
TRANCE protein
Tumor necrosis factor-TNF
Womens health
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Summary:Women with multiple sclerosis (MS) can safely become pregnant and give birth, with no side effects or impediments. Pregnancy is generally accepted as a period of well-being in which relapses have a softer evolution, particularly in the third trimester. Herein, we hypothesized that the placenta, via its "secretome", could contribute to the recognized beneficial effects of pregnancy on MS activity. We focused on a well-known receptor/ligand/decoy receptor system, such as the one composed by the receptor activator of nuclear factor-kB (RANK), its ligand (RANKL), and the decoy receptor osteoprotegerin (OPG), which have never been investigated in an integrated way in MS, pregnancy, and placenta. We reported that pregnancy at the term of gestation influences the balance between circulating RANKL and its endogenous inhibitor OPG in MS women. We demonstrated that the placenta at term is an invaluable source of homodimeric OPG. By functional studies on astrocytes, we showed that placental OPG suppresses the mRNA expression of the CCL20, a chemokine responsible for Th17 cell recruitment. We propose placental OPG as a crucial molecule for the recognized beneficial effect of late pregnancy on MS and its potential utility for the development of new and more effective therapeutic approaches.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11081357