The G protein-coupled estrogen receptor (GPER) agonist G-1 expands the regulatory T-cell population under TH17-polarizing conditions

J Immunother. 2013 Apr;36(3):190-6. doi: 10.1097/CJI.0b013e31828d8e3b.


The transcription factor Foxp3 is critical to the suppressive phenotype of CD4+ regulatory T cells. Studies have clearly shown that numerous autoimmune diseases are marked by the presence of activated CD4+ T cells within the setting of chronic inflammation. Therefore, drugs capable of inducing Foxp3 expression in activated CD4+ T cells could be of great therapeutic interest. We have previously shown that the small molecule G-1, an agonist directed against the membrane-bound G protein-coupled estrogen receptor, can induce IL10 expression in naive CD4+ T cells. In addition, we and others have demonstrated that G-1 attenuates disease in an animal model of experimental autoimmune encephalomyelitis. Using ex vivo cultures of purified CD4+ T cells, we show that G-1 can elicit Foxp3 expression under TH17-polarizing conditions, which mimic the in situ inflammatory milieu of several autoimmune diseases. These findings build upon previous results demonstrating the immunosuppressive properties of the novel estrogenic small molecule G-1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Cyclopentanes / pharmacology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Quinolines / pharmacology*
  • RNA, Messenger / biosynthesis
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / immunology*
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*


  • 1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone
  • Cyclopentanes
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • GPER1 protein, mouse
  • Quinolines
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled