Estrogen modulation of endosome-associated toll-like receptor 8 an IFNα-independent mechanism of sex-bias in systemic lupus erythematosus

Estrogen modulation of endosome-associated toll-like receptor 8 : an IFNα-independent mechanism of sex-bias in systemic lupus erythematosus

Copyright © 2014 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 151(2014), 1 vom: 01. März, Seite 66-77
1. Verfasser: Young, Nicholas A (VerfasserIn)
Weitere Verfasser: Wu, Lai-Chu, Burd, Craig J, Friedman, Alexandra K, Kaffenberger, Benjamin H, Rajaram, Murugesan V S, Schlesinger, Larry S, James, Hayley, Shupnik, Margaret A, Jarjour, Wael N
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2014
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Autoimmunity Estrogen Sex-bias Systemic lupus erythematosus Toll-like receptor ESR1 protein, human Estrogen Receptor alpha mehr... Imidazoles Immunologic Factors Interferon-alpha TLR8 protein, human Toll-Like Receptor 8 Estradiol 4TI98Z838E resiquimod V3DMU7PVXF
Beschreibung
Zusammenfassung:Copyright © 2014 Elsevier Inc. All rights reserved.
Females of child-bearing age are more resistant to infectious disease and have an increased risk of systemic lupus erythematosus (SLE). We hypothesized that estrogen-induced gene expression could establish an immunoactivated state which would render enhanced defense against infection, but may be deleterious in autoimmune development. Using peripheral blood mononuclear cells (PBMCs), we demonstrate enhanced responses with immunogen stimulation in the presence of 17β-estradiol (E2) and gene array analyses reveal toll-like receptor 8 (TLR8) as an E2-responsive candidate gene. TLR8 expression levels are up-regulated in SLE and PBMCs stimulated with TLR8 agonist display a female sex-biased, E2-sensitive response. Moreover, we identify a putative ERα-binding region near the TLR8 locus and blocking ERα expression significantly decreases E2-mediated TLR8 induction. Our findings characterize TLR8 as a novel estrogen target gene that can lower the inflammatory threshold and implicate an IFNα-independent inflammatory mechanism that could contribute to higher SLE incidence in women
Beschreibung:Date Completed 10.04.2014
Date Revised 21.10.2021
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2014.01.006