IL-15Rα of Radiation-Resistant Cells Is Necessary and Sufficient for Thymic Invariant NKT Cell Survival and Functional Maturation
IL-15Rα of Radiation-Resistant Cells Is Necessary and Sufficient for Thymic Invariant NKT Cell Survival and Functional Maturation
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DOI：
10.4049/jimmunol.1100270
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发表时间：
2011-08-01
影响因子：
4.4
通讯作者：
Liao, Nan-Shih
中科院分区：
文献类型：
--
作者：
Chang, Chin-Ling;Lai, Yein-Gei;Liao, Nan-Shih
不变NKT（iNKT）细胞的发育取决于胸腺。在通过CD 4 + CD 8 + CD 1d+皮质胸腺细胞进行阳性选择后，iNKT细胞从CD 44（低）NK1.1（-）（第1阶段）到CD 44（高）NK1.1（+）（第2阶段），然后到CD 44（高）NK1.1（+）（第3阶段）细胞。细胞因子产生的编程沿着三个分化阶段发生，而NK受体的获得发生在阶段3。第3阶段胸腺iNKT细胞在Il 15 ra（-/-）小鼠中特异性减少。这种稳态缺陷的机制以及IL-15系统是否影响其他胸腺iNKT细胞发育事件仍然难以捉摸。在这项研究中，我们证明了增加的细胞死亡导致了Il 15 ra（-/-）小鼠中3期细胞的减少，因为Bim的敲除恢复了该群体。3期细胞中Bcl-2的IL-15依赖性上调影响细胞存活，因为hBcl-2的过表达部分恢复了Il 15 ra（-/-）小鼠中的3期细胞。此外，Il 15 ra（-/-）小鼠中的胸腺iNKT细胞在功能成熟方面受损，包括Ly 49和NKG 2受体的获得以及细胞因子产生的编程。最后，由辐射抗性细胞表达的IL 15 R α对于支持胸腺iNKT细胞的存活以及所检查的成熟事件是必要的且足够的。免疫学杂志，2011，187：1235-1242。
The development of invariant NKT (iNKT) cells depends on the thymus. After positive selection by CD4+CD8+CD1d+ cortical thymocytes, iNKT cells proceed from CD44(low)NK1.1(-) (stage 1) to CD44(high)NK1.1(+) ( stage 2), and then to CD44(high)NK1.1(+) ( stage 3) cells. The programming of cytokine production occurs along the three differentiation stages, whereas the acquisition of NK receptors occurs at stage 3. Stage 3 thymic iNKT cells are specifically reduced in Il15ra(-/-) mice. The mechanism underlying this homeostatic deficiency and whether the IL-15 system affects other thymic iNKT cell developmental events remain elusive. In this study, we demonstrate that increased cell death contributed to the reduction of stage 3 cells in Il15ra(-/-) mice, as knockout of Bim restored this population. IL-15-dependent upregulation of Bcl-2 in stage 3 cells affected cell survival, as overexpression of hBcl-2 partially restored stage 3 cells in Il15ra(-/-) mice. Moreover, thymic iNKT cells in Il15ra(-/-) mice were impaired in functional maturation, including the acquisition of Ly49 and NKG2 receptors and the programming of cytokine production. Finally, IL15R alpha expressed by radiation-resistant cells is necessary and sufficient to support the survival as well as the examined maturation events of thymic iNKT cells. The Journal of Immunology, 2011, 187: 1235-1242.