Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Int J Oncol. 2011 Feb;38(2):547-53. doi: 10.3892/ijo.2010.870. Epub 2010 Dec 14.
The thymus is the major site of T cell differentiation and a key organ of the immune system. Thym atrophy has been observed in several model systems including aging, and tumor development. Previous results from our laboratory have reported that the thymic atrophy seen in mammary tumor bearers is associated with a severe depletion of CD4+CD8+ double positive immature cells and changes in the levels of cytokines expressed in the thymus microenvironment. Cytokines regulate numerous aspects of hematopoiesis via activation of the Jak/Stat pathways. In the present study we have used our mammary tumor model to investigate whether changes in the levels of cytokines in the thymus could affect the normal expression of the aforementioned pathways. RNA and protein analysis revealed an overexpression of the different members of interferons, a downregulation of most of the Jak/Stat pathways, and an increased expression of several suppressors of cytokine signaling (SOSC) in the thymuses of tumor bearers. Together, our data suggest that the impaired Jak/Stat signaling pathways observed in the whole thymus of tumor-bearing mice could be contributing to the abnormal T cell development and apoptosis observed during the tumor-induced thymic atrophy.
胸腺是 T 细胞分化的主要场所，也是免疫系统的关键器官。在包括衰老和肿瘤发展在内的几个模型系统中都观察到了胸腺萎缩。我们实验室之前的研究结果报告称，在乳腺癌患者中观察到的胸腺萎缩与 CD4+CD8+双阳性未成熟细胞的严重耗竭以及胸腺微环境中表达的细胞因子水平的变化有关。细胞因子通过激活 Jak/Stat 途径调节造血的众多方面。在本研究中，我们使用我们的乳腺癌模型来研究胸腺中细胞因子水平的变化是否会影响上述途径的正常表达。RNA 和蛋白质分析显示，干扰素的不同成员表达过度，大多数 Jak/Stat 途径下调，以及几种细胞因子信号转导抑制剂 (SOSC) 的表达增加。综上所述，我们的数据表明，在荷瘤小鼠的整个胸腺中观察到的受损 Jak/Stat 信号通路可能导致肿瘤诱导的胸腺萎缩过程中观察到的异常 T 细胞发育和凋亡。
