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

Speaker：陳澤思            Time：2003/12/03；13：00~14：00

Commentator：呂政展 老師              Place：Room 601

Abstract：

     Estrogen(E) as the key hormone for maintaining bone mass and E deficiency as the major cause of age-related bone loss in both sexes. At the cellular level, E affects the generation, lifespan, and functional activity of both osteoclasts and osteoblasts. E decreases osteoclast formation and activity by increasing apoptosis, it decreases osteoclast lifespan (1). In this study, authors showed that ovariectomy(ovx)-induced bone loss depends on the ability of estrogen deficiency to expand the number of TNF producing T cells. Furthermore, the data demonstrate that in vivo estrogen deficiency causes T cell expansion by enhancing T cell proliferation and lifespan. Both phenomena result from IFN-γ-mediated induction of CIITA in macrophage and T cells. Increased CIITA expression leads to augmented Ag presentation by macrophage, enhanced T cell activation, and increased activation dependent proliferation and lifespan of active T cells (2). In previously study ,that CIITA represses Fas ligand gene transcription and prevents CD4 T cell death mediated by the Fas：Fas ligand pathway upon activation (3).

Reference：

(1) Riggs, B. L., Khosla, S. & Melton, L. J., III .(2002).Sex Steroids and the Construction and Conservation of the Adult Skeleton. Endocrine Reviews 23(3):279–302

(2)Simone Cenci, Gianluca Toraldo, M. Neale Weitzmann.(2003). Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-γ-induced class II transactivator. PNAS 100(18)：10405–10410

(3)Gourley, T. S. & Chang, C. H. (2001).The Class II Transactivator Prevents Activation-Induced Cell Death by Inhibiting Fas Ligand Gene Expression.  J. Immunol. 166, 2917–2921.