An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency
An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency
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DOI：
10.1073/pnas.0505168102
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发表时间：
2005-11-15
影响因子：
11.1
通讯作者：
Pacifici, R
中科院分区：
文献类型：
--
作者：
Ryan, MR;Shepherd, R;Pacifici, R
雌激素缺乏引起的骨消耗部分是T细胞产生破骨细胞因子TNF-α增加的结果。这种现象是由于T细胞的扩增，但负责的机制是未知的。我们现在表明，卵巢切除术（ovx）失调T淋巴细胞生成和诱导骨丢失刺激，通过IL-7水平的上升，胸腺依赖分化的骨髓来源的祖细胞和胸腺独立，外周扩增的成熟T细胞。证明了胸腺效应的相关性，胸腺切除术减少了约50%的骨丢失和OVX诱导的T淋巴细胞生成的刺激。相比之下，体内升高的IL-7的衰减完全防止了T淋巴细胞生成的刺激和OVX后的骨丢失。因此，由OVX诱导的T细胞和骨稳态的破坏是由IL-7介导的，并且是由于胸腺和胸腺外机制。我们的结论是，IL-7是一个关键的上游目标，通过雌激素调节造血和免疫功能，骨稳态是至关重要的。
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 approximate to 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.