An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency.
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.
Ryan
Michaela Robbie
MR
Division of Endocrinology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Shepherd
Rebecca
R
Leavey
Jennifer K
JK
Gao
Yuhao
Y
Grassi
Francesco
F
Schnell
Frederick J
FJ
Qian
Wei-Ping
WP
Kersh
Gilbert J
GJ
Weitzmann
M Neale
MN
Pacifici
Roberto
R
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
D017931:DNA Primers; D004967:Estrogens; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha