Prenatal Betamethasone interferes with immune system development and alters target cells in autoimmune diabetes
Perna-Barrull, David (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodríguez-Fernández, Silvia (Institut Germans Trias i Pujol)
Pujol-Autonell, Irma (Institut Germans Trias i Pujol)
Gieras, A. (Department of Immunology. University Medical Center Hamburg-Eppendorf)
Ampudia Carrasco, Rosa María (Institut Germans Trias i Pujol)
Villalba Felipe, Adrián (Institut Germans Trias i Pujol)
Glau, L. (Department of Immunology. University Medical Center Hamburg-Eppendorf)
Tolosa, E. (Department of Immunology. University Medical Center Hamburg-Eppendorf)
Vives Pi, Marta (Institut Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Fecha:	2019
Resumen:	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.
Ayudas:	Instituto de Salud Carlos III PI15-00198
Nota:	Altres ajuts: This work has been co-financed with the European Regional Development funds (FEDER), and supported by the Deutsche Forschungsgemeinschaft (KFO296). CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) is an initiative from Instituto de Salud Carlos III. SRF is supported by the Agency for Management of University and Research Grants (AGAUR) of the Generalitat de Catalunya.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Animals ; Autoimmunity / drug effects* ; Betamethasone / administration & dosage* ; C-Peptide / immunology ; C-Peptide / metabolism ; Cell Survival / drug effects ; Cell Survival / immunology ; Diabetes Mellitus, Type 1 / immunology ; Diabetes Mellitus, Type 1 / prevention & control* ; Disease Models, Animal ; Female ; Glucocorticoids / administration & dosage* ; Humans ; Immune Tolerance / drug effects* ; Inclusion Bodies / drug effects ; Insulin-Secreting Cells / drug effects ; Insulin-Secreting Cells / immunology ; Insulin-Secreting Cells / metabolism ; Lymphocyte Activation ; Maternal Exposure ; Mice ; Mice, Inbred NOD ; Obstetric Labor, Premature / prevention & control ; Pregnancy
Publicado en:	Scientific reports, Vol. 9 Núm. 1 (january 2019) , p. 1235, ISSN 2045-2322

DOI: 10.1038/s41598-018-37878-9
PMID: 30718757

15 p, 4.1 MB

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