title: Emerging roles for the interferon-inducible p200-family proteins in sex bias in systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple organs. The disease is characterized by the production of pathogenic autoantibodies to DNA and certain nuclear antigens, chronic inflammation, and immune dysregulation. Genetic studies involving SLE patients and mouse models have indicated that multiple lupus susceptible genes contribute to the disease phenotype. Notably, the development of SLE in patients and in certain mouse models exhibits a strong sex bias. In addition, several lines of evidence indicates that activation of interferon-α (IFN-α) signaling in immune cells and alterations in the expression of certain immunomodulatory cytokines contribute to lupus pathogenesis. Studies have implicated factors, such as the X chromosomal gene dosage effect and the sex hormones, in gender bias in SLE. However, the molecular mechanisms remain unclear. Additionally, it remains unclear whether these factors influence the "IFN-signature," which is associated with SLE. In this regard, a mutually positive regulatory feedback loop between IFNs and estrogen receptor-α (ERα) has been identified in immune cells. Moreover, studies indicate that the expression of certain IFN-inducible p200-family proteins that act as innate immune sensors for cytosolic DNA is differentially regulated by sex hormones. In this review, we discuss how the modulation of the expression of the p200-family proteins in immune cells by sex hormones and IFNs contributes to sex bias in SLE. An improved understanding of the regulation and roles of the p200-family proteins in immune cells is critical to understand lupus pathogenesis as well as response (or the lack of it) to various therapies.
authors: Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio 45267, USA. divaker.choubey@uc.edu
authors: Divaker
authors: D
authors: Choubey
authors: Ravichandran
authors: R
authors: Panchanathan
authors: Xin
authors: X
authors: Duan
authors: Hongqi
authors: H
authors: Liu
authors: Hongzhu
authors: H
authors: Liu
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology*; D012737:Sex Factors
chemical_list: D012739:Gonadal Steroid Hormones; C101635:HIN-200 protein, human; D009687:Nuclear Proteins