title: An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency.
abstract: The bone wasting induced by estrogen deficiency is, in part, a consequence of increased T cell production of the osteoclastogenic cytokine TNF-alpha. This phenomenon is due to an expansion of T cells, but the responsible mechanism is unknown. We now show that ovariectomy (ovx) disregulates T lymphopoiesis and induces bone loss by stimulating, through a rise in IL-7 levels, both thymic-dependent differentiation of bone marrow-derived progenitors and thymic-independent, peripheral expansion of mature T cells. Attesting to the relevance of the thymic effects, thymectomy decreases by approximately 50% the bone loss and the stimulation of T lymphopoiesis induced by ovx. In contrast, in vivo attenuation of the elevated IL-7 completely prevents the stimulation of T lymphopoiesis and the bone loss that follow ovx. Thus, the disruption of both T cell and bone homeostasis induced by ovx is mediated by IL-7 and due to both the thymic and extrathymic mechanisms. We conclude that IL-7 is a pivotal upstream target through which estrogen regulates hematopoietic and immune functions that are critical for bone homeostasis.
authors.affiliation: Division of Endocrinology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Michaela Robbie
authors.initials: MR
authors.lastname: Ryan
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shepherd
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Leavey
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Gao
authors.forename: Francesco
authors.initials: F
authors.lastname: Grassi
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Schnell
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Qian
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Kersh
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacifici
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006706:Homeostasis; D015851:Interleukin-7 / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000209:etiology* / Q000276:immunology; D010052:Ovariectomy; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D017931:DNA Primers; D004967:Estrogens; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha