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Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):E181-E190. doi: 10.1073/pnas.1617115114. Epub 2017 Jan 3.

Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy.

Author information

1
Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
2
Experimentelle Feto-Maternale Medizin, Klinik für Geburtshilfe und Pränatalmedizin, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
3
Institut für Neuroimmunologie und Institut für Multiple Sklerose Forschung, Universitätsmedizin Göttingen, 37073 Goettingen, Germany.
4
Institut für Zelluläre und Molekulare Immunologie, Universitätsmedizin Göttingen, 37075 Goettingen, Germany.
5
Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Charité Universitätsmedizin, 12203 Berlin, Germany.
6
Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany; manuel.friese@zmnh.uni-hamburg.de.

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.

KEYWORDS:

Treg; autoimmunity; multiple sclerosis; pregnancy; steroid hormones

PMID:
28049829
PMCID:
PMC5240705
DOI:
10.1073/pnas.1617115114
[Indexed for MEDLINE]
Free PMC Article

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