Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish through G Protein-Coupled Estrogen Receptor 1

Natural antibodies play crucial roles in pathogen elimination, B-cell survival and homeostasis, and inflammatory and autoimmune diseases. Although estrogens are able to regulate both innate and adaptive immune responses, their role in the production of natural antibodies is unknown. Here, we show th...

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Main Authors: María C. Rodenas, Isabel Cabas, Nuria E. Gómez-González, Marta Arizcun, José Meseguer, Victoriano Mulero, Alfonsa García-Ayala
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fimmu.2017.00736/full
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author María C. Rodenas
Isabel Cabas
Nuria E. Gómez-González
Marta Arizcun
José Meseguer
Victoriano Mulero
Alfonsa García-Ayala
author_facet María C. Rodenas
Isabel Cabas
Nuria E. Gómez-González
Marta Arizcun
José Meseguer
Victoriano Mulero
Alfonsa García-Ayala
author_sort María C. Rodenas
collection DOAJ
description Natural antibodies play crucial roles in pathogen elimination, B-cell survival and homeostasis, and inflammatory and autoimmune diseases. Although estrogens are able to regulate both innate and adaptive immune responses, their role in the production of natural antibodies is unknown. Here, we show that the dietary intake of the synthetic estradiol analog, 17α-ethinylestradiol (EE2), one of the most potent pharmaceutical estrogens and intensively used in human therapeutics as a component of most oral contraceptives, regulates the abundance and proliferation of T and IgM+ B lymphocytes in the teleost fish gilthead seabream (Sparus aurata L.). Furthermore, for the first time in vertebrates, it is shown that estrogen signaling through G protein-coupled estrogen receptor 1 (GPER1) induces the production of polyreactive natural antibodies, which are able to crossreact with unrelated antigens and commensal and pathogenic bacteria. In addition, the serum from fish treated with EE2 or the GPER1 agonist G1 shows higher complement-dependent bactericidal activity than that from non-treated specimens. These results demonstrate that estrogens and GPER1 are the key regulators of natural antibody production and pathogen clearance in fish, paving the way for future studies in other vertebrate classes.
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spelling doaj.art-9242c1579f2d444296d129ac1ec2c6b72022-12-22T00:48:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-06-01810.3389/fimmu.2017.00736276336Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish through G Protein-Coupled Estrogen Receptor 1María C. Rodenas0Isabel Cabas1Nuria E. Gómez-González2Marta Arizcun3José Meseguer4Victoriano Mulero5Alfonsa García-Ayala6Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, Murcia, SpainDepartment of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, Murcia, SpainDepartment of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, Murcia, SpainCentro Oceanográfico de Murcia, Instituto Español de Oceanografía (IEO), Murcia, SpainDepartment of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, Murcia, SpainDepartment of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, Murcia, SpainDepartment of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, Murcia, SpainNatural antibodies play crucial roles in pathogen elimination, B-cell survival and homeostasis, and inflammatory and autoimmune diseases. Although estrogens are able to regulate both innate and adaptive immune responses, their role in the production of natural antibodies is unknown. Here, we show that the dietary intake of the synthetic estradiol analog, 17α-ethinylestradiol (EE2), one of the most potent pharmaceutical estrogens and intensively used in human therapeutics as a component of most oral contraceptives, regulates the abundance and proliferation of T and IgM+ B lymphocytes in the teleost fish gilthead seabream (Sparus aurata L.). Furthermore, for the first time in vertebrates, it is shown that estrogen signaling through G protein-coupled estrogen receptor 1 (GPER1) induces the production of polyreactive natural antibodies, which are able to crossreact with unrelated antigens and commensal and pathogenic bacteria. In addition, the serum from fish treated with EE2 or the GPER1 agonist G1 shows higher complement-dependent bactericidal activity than that from non-treated specimens. These results demonstrate that estrogens and GPER1 are the key regulators of natural antibody production and pathogen clearance in fish, paving the way for future studies in other vertebrate classes.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00736/fullG protein-coupled estrogen receptor 1estrogenslymphocytesnatural antibodiesevolutionfish
spellingShingle María C. Rodenas
Isabel Cabas
Nuria E. Gómez-González
Marta Arizcun
José Meseguer
Victoriano Mulero
Alfonsa García-Ayala
Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish through G Protein-Coupled Estrogen Receptor 1
Frontiers in Immunology
G protein-coupled estrogen receptor 1
estrogens
lymphocytes
natural antibodies
evolution
fish
title Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish through G Protein-Coupled Estrogen Receptor 1
title_full Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish through G Protein-Coupled Estrogen Receptor 1
title_fullStr Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish through G Protein-Coupled Estrogen Receptor 1
title_full_unstemmed Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish through G Protein-Coupled Estrogen Receptor 1
title_short Estrogens Promote the Production of Natural Neutralizing Antibodies in Fish through G Protein-Coupled Estrogen Receptor 1
title_sort estrogens promote the production of natural neutralizing antibodies in fish through g protein coupled estrogen receptor 1
topic G protein-coupled estrogen receptor 1
estrogens
lymphocytes
natural antibodies
evolution
fish
url http://journal.frontiersin.org/article/10.3389/fimmu.2017.00736/full
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