Prenatal Betamethasone interferes with immune system development and alters target cells in autoimmune diabetes

David Perna-Barrull, Silvia Rodriguez-Fernandez, Irma Pujol-Autonell, Anna Gieras, Rosa M. Ampudia-Carrasco, Adrian Villalba, Laura Glau, Eva Tolosa, Marta Vives-Pi

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2 Citations (Scopus)

Abstract

© 2019, The Author(s). Non-genetic factors are crucial in the pathogenesis of type 1 diabetes (T1D), a disease caused by autoimmunity against insulin-producing β-cells. Exposure to medications in the prenatal period may influence the immune system maturation, thus altering self-tolerance. Prenatal administration of betamethasone –a synthetic glucocorticoid given to women at risk of preterm delivery– may affect the development of T1D. It has been previously demonstrated that prenatal betamethasone administration protects offspring from T1D development in nonobese diabetic (NOD) mice. The direct effect of betamethasone on the immature and mature immune system of NOD mice and on target β-cells is analysed in this paper. In vitro, betamethasone decreased lymphocyte viability and induced maturation-resistant dendritic cells, which in turn impaired γδ T cell proliferation and decreased IL-17 production. Prenatal betamethasone exposure caused thymus hypotrophy in newborn mice as well as alterations in immune cells subsets. Furthermore, betamethasone decreased β-cell growth, reduced C-peptide secretion and altered the expression of genes related to autoimmunity, metabolism and islet mass in T1D target tissue. These results support the protection against T1D in the betamethasone-treated offspring and demonstrate that this drug alters the developing immune system and β-cells. Understanding how betamethasone generates self-tolerance could have potential clinical relevance in T1D.
Original languageEnglish
Article number1235
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 1 Dec 2019

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    Perna-Barrull, D., Rodriguez-Fernandez, S., Pujol-Autonell, I., Gieras, A., Ampudia-Carrasco, R. M., Villalba, A., Glau, L., Tolosa, E., & Vives-Pi, M. (2019). Prenatal Betamethasone interferes with immune system development and alters target cells in autoimmune diabetes. Scientific Reports, 9, [1235]. https://doi.org/10.1038/s41598-018-37878-9