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Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity

Prenatal glucocorticoids are routinely administered to pregnant women at risk of preterm delivery in order to improve survival of the newborn. However, in half of the cases, birth occurs outside the beneficial period for lung development. Glucocorticoids are potent immune modulators and cause apopto...

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Autores principales: Gieras, Anna, Gehbauer, Christina, Perna-Barrull, David, Engler, Jan Broder, Diepenbruck, Ines, Glau, Laura, Joosse, Simon A., Kersten, Nora, Klinge, Stefanie, Mittrücker, Hans-Willi, Friese, Manuel A., Vives-Pi, Marta, Tolosa, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693859/
https://www.ncbi.nlm.nih.gov/pubmed/29181000
http://dx.doi.org/10.3389/fimmu.2017.01505
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author Gieras, Anna
Gehbauer, Christina
Perna-Barrull, David
Engler, Jan Broder
Diepenbruck, Ines
Glau, Laura
Joosse, Simon A.
Kersten, Nora
Klinge, Stefanie
Mittrücker, Hans-Willi
Friese, Manuel A.
Vives-Pi, Marta
Tolosa, Eva
author_facet Gieras, Anna
Gehbauer, Christina
Perna-Barrull, David
Engler, Jan Broder
Diepenbruck, Ines
Glau, Laura
Joosse, Simon A.
Kersten, Nora
Klinge, Stefanie
Mittrücker, Hans-Willi
Friese, Manuel A.
Vives-Pi, Marta
Tolosa, Eva
author_sort Gieras, Anna
collection PubMed
description Prenatal glucocorticoids are routinely administered to pregnant women at risk of preterm delivery in order to improve survival of the newborn. However, in half of the cases, birth occurs outside the beneficial period for lung development. Glucocorticoids are potent immune modulators and cause apoptotic death of immature T cells, and we have previously shown that prenatal betamethasone treatment at doses eliciting lung maturation induce profound thymocyte apoptosis in the offspring. Here, we asked if there are long-term consequences on the offspring’s immunity after this treatment. In the non-obese diabetic mouse model, prenatal betamethasone clearly decreased the frequency of pathogenic T cells and the incidence of type 1 diabetes (T1D). In contrast, in the lupus-prone MRL/lpr strain, prenatal glucocorticoids induced changes in the T cell repertoire that resulted in more autoreactive cells. Even though glucocorticoids transiently enhanced regulatory T cell (Treg) development, these cells did not have a protective effect in a model for multiple sclerosis which relies on a limited repertoire of pathogenic T cells for disease induction that were not affected by prenatal betamethasone. We conclude that prenatal steroid treatment, by inducing changes in the T cell receptor repertoire, has unforeseeable consequences on development of autoimmune disease. Our data should encourage further research to fully understand the consequences of this widely used treatment.
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spelling pubmed-56938592017-11-27 Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity Gieras, Anna Gehbauer, Christina Perna-Barrull, David Engler, Jan Broder Diepenbruck, Ines Glau, Laura Joosse, Simon A. Kersten, Nora Klinge, Stefanie Mittrücker, Hans-Willi Friese, Manuel A. Vives-Pi, Marta Tolosa, Eva Front Immunol Immunology Prenatal glucocorticoids are routinely administered to pregnant women at risk of preterm delivery in order to improve survival of the newborn. However, in half of the cases, birth occurs outside the beneficial period for lung development. Glucocorticoids are potent immune modulators and cause apoptotic death of immature T cells, and we have previously shown that prenatal betamethasone treatment at doses eliciting lung maturation induce profound thymocyte apoptosis in the offspring. Here, we asked if there are long-term consequences on the offspring’s immunity after this treatment. In the non-obese diabetic mouse model, prenatal betamethasone clearly decreased the frequency of pathogenic T cells and the incidence of type 1 diabetes (T1D). In contrast, in the lupus-prone MRL/lpr strain, prenatal glucocorticoids induced changes in the T cell repertoire that resulted in more autoreactive cells. Even though glucocorticoids transiently enhanced regulatory T cell (Treg) development, these cells did not have a protective effect in a model for multiple sclerosis which relies on a limited repertoire of pathogenic T cells for disease induction that were not affected by prenatal betamethasone. We conclude that prenatal steroid treatment, by inducing changes in the T cell receptor repertoire, has unforeseeable consequences on development of autoimmune disease. Our data should encourage further research to fully understand the consequences of this widely used treatment. Frontiers Media S.A. 2017-11-13 /pmc/articles/PMC5693859/ /pubmed/29181000 http://dx.doi.org/10.3389/fimmu.2017.01505 Text en Copyright © 2017 Gieras, Gehbauer, Perna-Barrull, Engler, Diepenbruck, Glau, Joosse, Kersten, Klinge, Mittrücker, Friese, Vives-Pi and Tolosa. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor 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.
spellingShingle Immunology
Gieras, Anna
Gehbauer, Christina
Perna-Barrull, David
Engler, Jan Broder
Diepenbruck, Ines
Glau, Laura
Joosse, Simon A.
Kersten, Nora
Klinge, Stefanie
Mittrücker, Hans-Willi
Friese, Manuel A.
Vives-Pi, Marta
Tolosa, Eva
Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity
title Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity
title_full Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity
title_fullStr Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity
title_full_unstemmed Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity
title_short Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity
title_sort prenatal administration of betamethasone causes changes in the t cell receptor repertoire influencing development of autoimmunity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693859/
https://www.ncbi.nlm.nih.gov/pubmed/29181000
http://dx.doi.org/10.3389/fimmu.2017.01505
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