title: The G protein-coupled estrogen receptor (GPER) agonist G-1 expands the regulatory T-cell population under TH17-polarizing conditions.
abstract: 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.
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Brunsing
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Owens
authors.forename: Eric R
authors.initials: ER
authors.lastname: Prossnitz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C532507:GPER1 protein, mouse; D011804:Quinolines; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled