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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)10405-10410
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number18
DOIs
Publication statusPublished - Sep 2 2003

Keywords

  • Osteoporosis
  • Ovariectomy
  • Sex steroids
  • Tumor necrosis factor

ASJC Scopus subject areas

  • General
  • Genetics

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