title: Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy.
abstract: Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In vitro, we found the pregnancy hormone progesterone to robustly increase Treg frequencies via promiscuous binding to the glucocorticoid receptor (GR) in T cells. In vivo, T-cell-specific GR deletion in pregnant animals undergoing experimental autoimmune encephalomyelitis (EAE), the animal model of MS, resulted in a reduced Treg increase and a selective loss of pregnancy-induced protection, whereas reproductive success was unaffected. Our data imply that steroid hormones can shift the immunological balance in favor of Tregs via differential engagement of the GR in T cells. This newly defined mechanism confers protection from autoimmunity during pregnancy and represents a potential target for future therapy.
authors.affiliation: Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Jan Broder
authors.initials: JB
authors.lastname: Engler
authors.affiliation: Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Kursawe
authors.affiliation: Experimentelle Feto-Maternale Medizin, Klinik für Geburtshilfe und Pränatalmedizin, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: María Emilia
authors.initials: ME
authors.lastname: Solano
authors.affiliation: Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Kostas
authors.initials: K
authors.lastname: Patas
authors.affiliation: Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wehrmann
authors.affiliation: Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Heckmann
authors.affiliation: Institut für Neuroimmunologie und Institut für Multiple Sklerose Forschung, Universitätsmedizin Göttingen, 37073 Goettingen, Germany.
authors.forename: Fred
authors.initials: F
authors.lastname: Lühder
authors.affiliation: Institut für Zelluläre und Molekulare Immunologie, Universitätsmedizin Göttingen, 37075 Goettingen, Germany.
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.affiliation: Experimentelle Feto-Maternale Medizin, Klinik für Geburtshilfe und Pränatalmedizin, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Petra Clara
authors.initials: PC
authors.lastname: Arck
authors.affiliation: Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.|Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Charité Universitätsmedizin, 12203 Berlin, Germany.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Gold
authors.affiliation: Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany; manuel.friese@zmnh.uni-hamburg.de.
authors.forename: Manuel A
authors.identifier: 0000-0001-6380-2420
authors.initials: MA
authors.lastname: Friese
mesh_terms: D000818:Animals; D015551:Autoimmunity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D008810:Mice, Inbred C57BL; D011247:Pregnancy / Q000276:immunology*; D011374:Progesterone / Q000276:immunology; D011965:Receptors, Glucocorticoid / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011965:Receptors, Glucocorticoid; D011374:Progesterone
keywords: Treg; autoimmunity; multiple sclerosis; pregnancy; steroid hormones