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Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-γ-induced class II transactivator

By Simone Cenci, Gianluca Toraldo, M. Neale Weitzmann, Cristiana Roggia, Yuhao Gao, Wei Ping Qian, Oscar Sierra and Roberto Pacifici

Abstract

Expansion of the pool of tumor necrosis factor (TNF)-α-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-γ-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-γ 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-γ receptor signaling. Thus, increased IFN-γ-induced class II transactivator expression and the resulting enhanced T cell proliferation and lifespan are critical to the bone wasting effect of estrogen deficiency

Topics: Biological Sciences
Publisher: National Academy of Sciences
Year: 2003
DOI identifier: 10.1073/pnas.1533207100
OAI identifier: oai:pubmedcentral.nih.gov:193574
Provided by: PubMed Central
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