IL-15 regulates homeostasis and terminal maturation of NKT cells.
IL-15 regulates homeostasis and terminal maturation of NKT cells.
复制标题
DOI：
10.4049/jimmunol.1003965
复制
发表时间：
2011-12-15
期刊：
影响因子：
--
通讯作者：
Joyce S
中科院分区：
文献类型：
--
作者：
Gordy LE;Bezbradica JS;Flyak AI;Spencer CT;Dunkle A;Sun J;Stanic AK;Boothby MR;He YW;Zhao Z;Van Kaer L;Joyce S
半不变自然杀伤T （NKT）细胞是胸腺来源的先天淋巴细胞，调节微生物和肿瘤免疫以及自身免疫性疾病。NKT细胞的这些免疫调节特性是在其发育过程中获得的。关于促进NKT细胞发育的分子和细胞线索，我们已经了解了很多，但这些细胞如何在胸腺和周围维持，以及它们如何获得功能能力，我们还不完全了解。我们发现IL-15在体外胸腺和脾脏NKT细胞中诱导多种Bcl-2家族存活因子。然而，il15介导的胸腺和外周NKT细胞的存活严重依赖于Bcl-xL的表达。此外，IL-15调节胸腺发育阶段2 （ST2）到ST3谱系的进展和终末NKT细胞分化。全球基因表达分析和验证表明，IL-15调节胸腺NKT细胞中Tbx21 （T-bet）的表达。IL15的缺失还导致NKT细胞中IFN-γ、颗粒酶A、C等关键效应分子以及几种NK细胞受体表达不良。综上所述，我们的研究结果揭示了IL-15在由Bcl-xL介导的NKT细胞存活和效应分化中起关键作用，这与T-bet在调节终末成熟中的作用是一致的。
Semi-invariant natural killer T (NKT) cells are thymus-derived innate lymphocytes that modulate microbial and tumour immunity as well as autoimmune diseases. These immunoregulatory properties of NKT cells are acquired during their development. Much has been learnt regarding the molecular and cellular cues that promote NKT cell development, yet how these cells are maintained in the thymus and the periphery and how they acquire functional competence are incompletely understood. We found that IL-15 induced several Bcl-2 family survival factors in thymic and splenic NKT cells in vitro. Yet, IL15-mediated thymic and peripheral NKT cell survival critically depended on Bcl-xL expression. Additionally, IL-15 regulated thymic developmental stage 2 (ST2) to ST3 lineage progression and terminal NKT cell differentiation. Global gene expression analyses and validation revealed that IL-15 regulated Tbx21 (T-bet) expression in thymic NKT cells. The loss of IL15 also resulted in poor expression of key effector molecules such as IFN-γ, granzyme A and C as well as several NK cell receptors in NKT cells. Taken together, our findings reveal a critical role for IL-15 in NKT cell survival, which is mediated by Bcl-xL, and effector differentiation, which is consistent with a role of T-bet in regulating terminal maturation.
登录
查看更多内容
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
30.5
作者：
D'Cruz, Louise M.;Knell, Jamie;Goldrath, Ananda W.
通讯作者：
Goldrath, Ananda W.
影响因子：
4.4
作者：
Berzins, Stuart P.;McNab, Finlay W.;Godfrey, Dale I.
通讯作者：
Godfrey, Dale I.
影响因子：
32.4
作者：
Egawa, T;Eberl, G;Littman, DR
通讯作者：
Littman, DR
影响因子：
4.4
作者：
Chang, Chin-Ling;Lai, Yein-Gei;Liao, Nan-Shih
通讯作者：
Liao, Nan-Shih