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• W2092505499 abstract "Expansion of the pool of tumor necrosis factor (TNF)-alpha-producing T cells is instrumental for the bone loss induced by estrogen deficiency, but the responsible mechanism is unknown. Here we show that ovariectomy up-regulates IFN-gamma-induced class II transactivator, a multitarget immune modulator, resulting in increased antigen presentation by macrophages, enhanced T cell activation, and prolonged lifespan of active T cells. Up-regulation of class II transactivator derives from increased production of IFN-gamma by T helper 1 cells, resulting from enhanced secretion of IL-12 and IL-18 by macrophages. The resulting T cell expansion and bone loss are prevented in vivo by both blockade of antigen presenting cell-induced T cell activation, and silencing of IFN-gamma receptor signaling. Thus, increased IFN-gamma-induced class II transactivator expression and the resulting enhanced T cell proliferation and lifespan are critical to the bone wasting effect of estrogen deficiency." @default.
• W2092505499 created "2016-06-24" @default.
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• W2092505499 date "2003-08-15" @default.
• W2092505499 modified "2023-10-10" @default.
• W2092505499 title "Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-γ-induced class II transactivator" @default.
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• W2092505499 doi "https://doi.org/10.1073/pnas.1533207100" @default.
• W2092505499 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/193574" @default.
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