title: Estrogen receptor-β ligand treatment modulates dendritic cells in the target organ during autoimmune demyelinating disease.
abstract: Estrogens act upon nuclear estrogen receptors (ER) to ameliorate cell-mediated autoimmune disease. As most immunomodulatory effects of estrogens in EAE have been attributed to the function of ER-α, we previously demonstrated that ER-β ligand treatment reduced disease severity without affecting peripheral cytokine production or levels of CNS inflammation, suggesting a direct neuroprotective effect; however, the effect of ER-β treatment on the function of immune cells within the target organ remained unknown. Here, we used adoptive transfer studies to show that ER-β ligand treatment was protective in the effector, but not the induction phase of EAE, as shown by decreased clinical disease severity with the preservation of axons and myelin in spinal cords. The analysis of the immune cell infiltrates in the CNS revealed that while ER-β ligand treatment did not reduce overall levels of CNS inflammation, there was a decrease in the DC percentage, and these CNS DC had decreased TNF-α production. Finally, experiments using DC deficient in ER-β revealed that the expression of ER-β on DC was essential for protective effects of ER-β ligand treatment in EAE. Our results demonstrate for the first time an effect of ER-β ligand treatment in vivo on DC in the target organ of a prototypic cell-mediated autoimmune disease.
authors.affiliation: UCLA Department of Physiological Sciences, Los Angeles, CA 90095, USA.
authors.forename: Sienmi
authors.initials: S
authors.lastname: Du
authors.forename: Francisco
authors.initials: F
authors.lastname: Sandoval
authors.forename: Pauline
authors.initials: P
authors.lastname: Trinh
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Umeda
authors.forename: Rhonda
authors.initials: R
authors.lastname: Voskuhl
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000276:immunology*; D005260:Female; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology; D009570:Nitriles / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047629:Estrogen Receptor beta; D008024:Ligands; D009570:Nitriles; D011422:Propionates; D014409:Tumor Necrosis Factor-alpha