Syndecan-1 identifies and controls the frequency of IL-17-producing naïve natural killer T (NKT17) cells in mice.
Syndecan-1 identifies and controls the frequency of IL-17-producing naïve natural killer T (NKT17) cells in mice.
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DOI：
10.1002/eji.201545532
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发表时间：
2015-11
影响因子：
5.4
通讯作者：
Hamad AR
中科院分区：
文献类型：
--
作者：
Dai H;Rahman A;Saxena A;Jaiswal AK;Mohamood A;Ramirez L;Noel S;Rabb H;Jie C;Hamad AR
不变自然杀伤T （iNKT）细胞识别糖脂作为抗原，并在胸腺发育时分化为NKT1 (IFN-γ), NKT2 （IL-4）和NKT17 （IL-17）功能亚群。控制这些功能子集之间平衡的机制知之甚少，部分原因是缺乏可区分的表面标记物。在这里，我们发现硫酸肝素蛋白多糖syndecan-1 （sdc1）是naïve胸腺NKT17细胞的特异性标记物，并且sdc1缺乏显著增加胸腺NKT17细胞，以牺牲NKT1细胞为代价，导致体外和体内iNKT细胞来源的IFN-γ受损。利用sdc1的表面表达来鉴定NKT17细胞，我们证实了NKT17细胞的组织定位差异和株间变异性，并发现NKT17细胞表达高TCRβ，优先使用Vβ8，并且对CD3/CD28刺激的敏感性高于对γ -GalCer的敏感性。这些发现为未处理小鼠naïve NKT17细胞的鉴定和可行分选提供了一种新的无创简单方法，并表明sdc1表达负调控稳态iNKT细胞。此外，他们为研究sdc1调节NKT17细胞的机制奠定了基础。
Invariant natural killer T (iNKT) cells recognize glycolipids as antigens and diversify into NKT1 (IFN-γ), NKT2 (IL-4), and NKT17 (IL-17) functional subsets while developing in the thymus. Mechanisms that govern the balance between these functional subsets are poorly understood due partly to the lack of distinguishing surface markers. Here we identified the heparan sulfate proteoglycan syndecan-1 (sdc1) as a specific marker of naïve thymic NKT17 cells and that sdc1 deficiency significantly increased thymic NKT17 cells at the expense of NKT1 cells, leading to impaired iNKT cell-derived IFN-γ, both in vitro and in vivo. Using surface expression of sdc1 to identify NKT17 cells, we confirmed differential tissue localization and interstrain variability of NKT17 cells and uncovered that NKT17 cells expressed high TCRβ, preferentially use Vβ8, and display high sensitivity to ɑ-GalCer than to CD3/CD28 stimulation. These findings provide a novel non-invasive simple method for identification and viable sorting of naïve NKT17 cells from unmanipulated mice and suggest that sdc1 expression negatively regulates homeostasis iNKT cells. In addition, they lay the groundwork for investigating the mechanisms by which sdc1 regulates NKT17 cells.