The induction of the lupus phenotype by estrogen is via an estrogen receptor-α-dependent pathway

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• 作者：Feng Feng ; Jennifer Nyl ; Michelle Banyai ; Arthur Tatum ; Allen E. Silverstone ; Jerrie Gavalchin
• 关键词：Lupus ; Estrogen receptor ; Estradiol ; ERα ; -deficient mouse ; Idiotypic-reactive T cells
• 刊名：Clinical Immunology
• 出版年：2010
• 出版时间：February 2010
• 年：2010
• 卷：134
• 期：2
• 页码：226-236
• 全文大小：953 K

文摘

In order to investigate the roles of ER subtypes in the estrogen-induced lupus phenotype, ERα-deficient (ERα^−/−) and wild-type mice (WT) were injected monthly with estradiol (E-2) starting at 8 weeks. In WT mice, E-2 treatment induced a lupus phenotype, with accelerated death and increased kidney damage, as well as Th2-type serum cytokine and autoantibody production. In contrast, only minimal changes were observed in ERα^−/− mice after E-2 treatment. In a separate study, we found that in immune cells of autoimmune-prone SNF₁ and non-autoimmune DBF₁ mice, both ERα and ERβ were differentially expressed and modulated by E-2. In SNF₁ mice, there were more CD4⁺ and CD8⁺ T cells constitutively expressing ERα, and the percentages of ERα+ dendritic cells and macrophages were increased after E-2 exposure compared to DBF₁ mice. Taken together, these observations strongly suggest a role for ERα in E-2-induced development of the lupus phenotype.