Prenatal administration of Betamethasone causes changes in the T cell receptor repertoire influencing Development of autoimmunity
Gieras, Anna (University Medical Center Hamburg-Eppendorf. Department of Immunology)
Gehbauer, Christina (University Medical Center Hamburg-Eppendorf. Department of Immunology)
Perna-Barrull, David (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Engler, Jan Broder (Institute of Neuroimmunology and Multiple Sclerosis. Center for Molecular Neurobiology Hamburg)
Diepenbruck, Ines (University Medical Center Hamburg-Eppendorf. Department of Immunology)
Glau, Laura (University Medical Center Hamburg-Eppendorf. Department of Immunology)
Joosse, Simon A. (University Medical Center Hamburg-Eppendorf. Department of Tumor Biology)
Kersten, Nora (University Medical Center Hamburg-Eppendorf. Department of Immunology)
Klinge, Stefanie (University Medical Center Hamburg-Eppendorf. Department of Immunology)
Mittrücker, Hans-Willi (University Medical Center Hamburg-Eppendorf. Department of Immunology)
Friese, Manuel A. (Institute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg)
Vives Pi, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Tolosa, Eva (University Medical Center Hamburg-Eppendorf. Department of Immunology)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	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.
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Glucocorticoids ; Prenatal betamethasone ; T cell repertoire ; Autoimmunity ; Type 1 diabetes ; Non-obese diabetic mice ; Experimental autoimmune encephalomyelitis mice ; MRL/lpr
Published in:	Frontiers in immunology, Vol. 8 (november 2017) , p. 1-15, ISSN 1664-3224

DOI: 10.3389/fimmu.2017.01505
PMID: 29181000

15 p, 5.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
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