title: Estrogen receptor alpha signaling promotes Sle1-induced loss of tolerance and immune cell activation and is responsible for sex bias in B6.Sle1 congenic mice.
abstract: Sex bias in lupus incidence is thought to be due, in part, to the ability of estrogens to promote loss of tolerance. Previously, we showed that estrogens promote lupus via estrogen receptor α (ERα). C57BL/6 (B6) mice carrying the Sle1 lupus susceptibility locus (B6.Sle1) display loss of tolerance and develop anti-nuclear antibodies and immune cell hyperactivation. The incidence of loss of tolerance in B6.Sle1 females is greater than in males. Here, we show that a deficiency of either estrogens or ERα attenuates loss of tolerance and autoantibody development in B6.Sle1 females. Furthermore, we demonstrate that immune cell activation in B6.Sle1 mice shows sex bias and that ERα deficiency diminishes this phenotype in B6.Sle1 females. Thus, estrogens, acting via ERα, control sex bias in the Sle1 phenotype. Furthermore, we show that ERα may impact the Sle1 phenotype by modulating the expression of Pbx1, one of genes that underlies the Sle1 locus.
authors: Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE 68198-5805, USA.
authors: Shayla D
authors: SD
authors: Yoachim
authors: Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE 68198-5805, USA.
authors: Jenny S
authors: JS
authors: Nuxoll
authors: Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE 68198-5805, USA.
authors: Kimberly K
authors: KK
authors: Bynoté
authors: Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE 68198-5805, USA. Electronic address: kagould@unmc.edu.
authors: Karen A
authors: KA
authors: Gould
mesh_terms: D000818:Animals; D000939:Epitopes; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012737:Sex Factors; D015398:Signal Transduction
chemical_list: D000939:Epitopes; D047628:Estrogen Receptor alpha; D004967:Estrogens
keywords: Estrogen receptor alpha; Immune cell activation; Immunologic tolerance; Lupus; Sex bias