Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.
Immunol Lett. 2012 Dec 17;148(2):163-71. doi: 10.1016/j.imlet.2012.10.006. Epub 2012 Oct 17.
Lipid rafts have been shown to play significant roles in thymocyte development. However, the exact role of lipid rafts in single positive (SP) thymocyte differentiation is poorly characterized. We previously defined a developmental program (SP1→SP4) for CD4SP thymocytes. In this study, we found that lipid raft components were up-regulated during CD4SP maturation. Qa-2, a unique marker for the most mature SP4 subset, was localized to lipid rafts and heterogeneously expressed in SP4 cells. Functional assays showed that the proliferation capacity of SP4 cells correlated with the expression of Qa-2. Raft-disruption on both CD4SP and epithelial cells by cholesterol extraction or cholesterol oxidation in a medullary thymic epithelial cell (mTEC)-supported co-culture system impaired the transition from SP3 to SP4. This result was further confirmed in fetal thymic organ culture system. Collectively, these studies suggest that raft-associated signaling between mTECs and thymocytes drives the differentiation of CD4SP thymocytes and lipid rafts are involved in the final maturation of SP4 thymocytes.
脂质筏在胸腺细胞发育中发挥着重要作用。然而，脂质筏在单阳性 (SP) 胸腺细胞分化中的确切作用还没有得到很好的描述。我们之前定义了 CD4SP 胸腺细胞的一个发育程序 (SP1→SP4)。在这项研究中，我们发现脂质筏成分在 CD4SP 成熟过程中上调。Qa-2 是最成熟的 SP4 亚群的独特标志物，定位于脂质筏中，并在 SP4 细胞中不均匀表达。功能分析表明，SP4 细胞的增殖能力与 Qa-2 的表达相关。在髓质胸腺上皮细胞 (mTEC) 支持的共培养系统中，通过胆固醇提取或胆固醇氧化破坏 CD4SP 和上皮细胞上的筏，会损害从 SP3 到 SP4 的转化。这一结果在胎胸腺器官培养系统中得到了进一步证实。总之，这些研究表明 mTEC 和胸腺细胞之间与筏相关的信号转导驱动 CD4SP 胸腺细胞的分化，并且脂质筏参与了 SP4 胸腺细胞的最终成熟。
