title: The role of T lymphocytes in bone metabolism.
abstract: Recent findings from animal models suggest that the bone loss induced by estrogen deficiency may stem in large measure from a pathological upregulation of the adaptive immune response. While the role of activated T cells in the osteoporosis driven by inflammatory conditions and infection has been well documented, only recently has the role of T cells in the bone destruction associated with estrogen deficiency begun to be appreciated. In vivo and in vitro models of postmenopausal osteoporosis demonstrate that estrogen deficiency leads to an increase in the adaptive immune function that culminates in an increased production of tumor necrosis factor alpha (TNF) by activated T cells. TNF increases osteoclast (OC) formation and bone resorption both directly and by augmenting the sensitivity of maturing OCs to the essential osteoclastogenic factor receptor activator of nuclear factor kappaB ligand. The activation and expansion of TNF-producing T cells are key steps in estrogen deficiency-driven bone loss and are regulated by multiple interacting cytokines including transforming growth factor-beta, interleukin-7, and interferon-gamma, as well as by the process of antigen presentation. Herein, we review the experimental evidence that suggests estrogen prevents bone loss by regulating T-cell function and immune cell bone interactions.
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacifici
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000209:etiology; D001842:Bone and Bones / Q000378:metabolism*; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D010010:Osteoclasts / Q000502:physiology; D010024:Osteoporosis / Q000209:etiology; D010052:Ovariectomy; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004967:Estrogens; D014409:Tumor Necrosis Factor-alpha