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

Shayla D Yoachim, Jenny S. Nuxoll, Kimberly K. Bynoté, Karen A Gould

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)153-166
Number of pages14
JournalClinical Immunology
Volume158
Issue number2
DOIs
StatePublished - Jun 1 2015

Fingerprint

Congenic Mice
Safe Sex
Sexism
Immune Tolerance
Estrogen Receptor alpha
Estrogen Receptors
Estrogens
Phenotype
Aptitude
Incidence
Autoantibodies
Anti-Idiotypic Antibodies
Genes

Keywords

  • Estrogen receptor alpha
  • Immune cell activation
  • Immunologic tolerance
  • Lupus
  • Sex bias

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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. / Yoachim, Shayla D; Nuxoll, Jenny S.; Bynoté, Kimberly K.; Gould, Karen A.

In: Clinical Immunology, Vol. 158, No. 2, 01.06.2015, p. 153-166.

Research output: Contribution to journalArticle

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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.",
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