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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >c-Met signalling is required for efficient postnatal thymic regeneration and repair
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c-Met signalling is required for efficient postnatal thymic regeneration and repair

机译：有效的产后胸腺再生和修复需要c-Met信号传导

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摘要

We have reported that in vivo administration of the hybrid cytokine rIL-7/HGF or rIL-7/HGF, which contains interleukin-7 (IL-7) and the - or -chain of hepatocyte growth factor (HGF), significantly enhances thymopoiesis in mice after bone marrow transplantation. We have shown that the HGF receptor, c-Met, is involved in the effect of the hybrid cytokines. To address the role of c-Met signalling in thymocyte development and recovery, we generated conditional knockout (cKO) mice in which c-Met was specifically deleted in T cells by crossing c-Met(ft/ft) mice with CD4-Cre transgenic mice. We show here that although the number of total thymocytes and thymocyte subsets in young c-Met cKO mice is comparable to age-matched control (Ctrl) mice, the cKO mice were more susceptible to sub-lethal irradiation and dexamethasone treatment. This was demonstrated by low recovery in thymic cellularity in c-Met cKO mice after insult. Furthermore, the number of total thymocytes and thymocyte subsets was markedly reduced in 6- to 12-month-old cKO mice compared with age-matched Ctrl mice, and the thymic architecture of 12-month-old cKO mice was similar to that of 20-month-old wild-type mice. In addition, c-Met deficiency reduced cell survival and the expression of Bcl-xL in double-positive thymocytes, and decreased cell proliferation and the expression of cyclin E and cyclin-dependent kinase 5 in single-positive thymocytes. Our data indicate that c-Met signalling plays an important role in thymic regeneration after thymic insult. In addition, T-cell-specific inactivation of c-Met accelerates age-related thymic involution.
机译：我们已经报道，体内施用包含白介素7（IL-7）和肝细胞生长因子（HGF）-或-链的杂交细胞因子rIL-7 / HGF或rIL-7 / HGF可以显着增强胸腺造血功能在骨髓移植后的小鼠中。我们已经表明，HGF受体c-Met参与了杂交细胞因子的作用。为了解决c-Met信号传导在胸腺细胞发育和恢复中的作用，我们生成了条件敲除（cKO）小鼠，其中通过将c-Met（ft / ft）小鼠与CD4-Cre转基因杂交，从而在T细胞中特异性删除了c-Met老鼠。我们在这里显示，尽管年轻的c-Met cKO小鼠的总胸腺细胞和胸腺细胞亚群的数量与年龄匹配的对照（Ctrl）小鼠相当，但cKO小鼠更容易受到亚致死量照射和地塞米松治疗。损伤后，c-Met cKO小鼠的胸腺细胞性恢复较弱，这证明了这一点。此外，与年龄相匹配的Ctrl小鼠相比，6至12个月大的cKO小鼠的总胸腺细胞和胸腺细胞亚群的数量明显减少，并且12个月大的cKO小鼠的胸腺结构类似于20个月大的野生型小鼠。此外，c-Met缺乏症会降低双阳性胸腺细胞的细胞存活率和Bcl-xL的表达，并降低单阳性胸腺细胞的细胞增殖以及细胞周期蛋白E和细胞周期蛋白依赖性激酶5的表达。我们的数据表明，c-Met信号传导在胸腺损伤后的胸腺再生中起着重要作用。此外，c-Met的T细胞特异性失活会加速与年龄有关的胸腺退化。

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