An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency

Michaela Robbie Ryan, Rebecca Shepherd, Jennifer K. Leavey, Yuhao Gao, Francesco Grassi, Frederick J. Schnell, Wei Ping Qian, Gilbert J. Kersh, M. Neale Weitzmann, Roberto Pacifici

Research output: Contribution to journalArticle

Abstract

The bone wasting induced by estrogen deficiency is, in part, a consequence of increased T cell production of the osteoclastogenic cytokine TNF-α. 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 ≈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.

Original languageEnglish
Pages (from-to)16735-16740
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number46
DOIs
Publication statusPublished - Nov 15 2005

Keywords

  • Osteoporosis
  • Ovariectomized
  • Thymus
  • TNF-α

ASJC Scopus subject areas

  • Genetics
  • General

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    Ryan, M. R., Shepherd, R., Leavey, J. K., Gao, Y., Grassi, F., Schnell, F. J., Qian, W. P., Kersh, G. J., Weitzmann, M. N., & Pacifici, R. (2005). An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency. Proceedings of the National Academy of Sciences of the United States of America, 102(46), 16735-16740. https://doi.org/10.1073/pnas.0505168102