Membrane estrogen receptor regulates experimental autoimmune encephalomyelitis through up-regulation of programmed death 1

Chunhe Wang, Babak Dehghani, Yuexin Li, Laurie J. Kaler, Thomas Proctor, Arthur Vandenbark, Halina Offner

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Abstract

Although estrogens exert a pronounced protective effect on multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), their therapeutic application has been limited by undesirable side effects thought to be mediated primarily through estradiol binding to intracellular estrogen receptor α. In this study, we found that signaling through the putative membrane estrogen receptor, G protein-coupled receptor 30 (GPR30), was sufficient to mediate protection against EAE, which was significantly impaired in GPR30 gene-deficient mice. Treatment with G-1, an agonist that selectively activates GPR30 without engagement of the intracellular estrogen receptors, retained the ability of estradiol to protect against clinical and histological EAE without estradiol-associated side effects, deviated cytokine profiles, and enhanced suppressive activity of CD4+Foxp3+ T regulatory cells through a GPR30- and programmed death 1-dependent mechanism. This study is the first to evaluate the protective effect of GPR30 activation on EAE, and provides a strong foundation for the clinical application of GPR30 agonists such as G-1 in multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)3294-3303
Number of pages10
JournalJournal of Immunology
Volume182
Issue number5
DOIs
StatePublished - Mar 1 2009

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Autoimmune Experimental Encephalomyelitis
G-Protein-Coupled Receptors
Estrogen Receptors
Up-Regulation
Membranes
Estradiol
Multiple Sclerosis
Regulatory T-Lymphocytes
Estrogens
Animal Models
Cytokines
Genes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Membrane estrogen receptor regulates experimental autoimmune encephalomyelitis through up-regulation of programmed death 1. / Wang, Chunhe; Dehghani, Babak; Li, Yuexin; Kaler, Laurie J.; Proctor, Thomas; Vandenbark, Arthur; Offner, Halina.

In: Journal of Immunology, Vol. 182, No. 5, 01.03.2009, p. 3294-3303.

Research output: Contribution to journalArticle

Wang, Chunhe ; Dehghani, Babak ; Li, Yuexin ; Kaler, Laurie J. ; Proctor, Thomas ; Vandenbark, Arthur ; Offner, Halina. / Membrane estrogen receptor regulates experimental autoimmune encephalomyelitis through up-regulation of programmed death 1. In: Journal of Immunology. 2009 ; Vol. 182, No. 5. pp. 3294-3303.
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