Slamf1, the NKT cell control gene Nkt1

Slamf1, the NKT cell control gene Nkt1
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DOI:
10.4049/jimmunol.178.3.1618
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发表时间:
2007-02-01
影响因子:
4.4
通讯作者:
Baxter, Alan G.
Baxter, Alan G.
中科院分区:
医学2区
文献类型:
--
作者:
Jordan, Margaret A.;Fletcher, Julie M.;Baxter, Alan G.

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不变性NKT细胞在控制适应性免疫反应的强度和特征方面起着关键作用。我们之前报道了NOD小鼠品系中NKT细胞数量和功能的缺陷,NOD小鼠品系是1型糖尿病和系统性红斑狼疮的良好验证模型。胸腺NKT细胞数量的遗传控制定位于两个连锁区域:1号染色体远端Nkt1和2号染色体上的Nkt2。在这项研究中,我们报道了一个NOD.Nkrp1的产生和表征(b)。Nkt1(b)同源小鼠菌株,应用微阵列表达分析将候选基因限制在95%置信范围内,确定了Slamf1(编码信号淋巴细胞激活分子)和Slamf6(编码Ly108)作为潜在候选基因,并证明NOD小鼠T细胞发育过程中信号淋巴细胞激活分子表达迟缓,导致CD4(+)CD8(+)阶段表达减少。这与NOD小鼠NKT细胞生成减少和耐受诱导紊乱一致。
Invariant NKT cells play a critical role in controlling the strength and character of adaptive immune responses. We have previously reported deficiencies in the numbers and function of NKT cells in the NOD mouse strain, which is a well-validated model of type 1 diabetes and systemic lupus erythematosus. Genetic control of thymic NKT cell numbers was mapped to two linkage regions: Nkt1 on distal chromosome 1 and Nkt2 on chromosome 2. In this study, we report the production and characterization of a NOD.Nkrp1(b).Nkt1(b) congenic mouse strain, apply microarray expression analyses to limit candidate genes within the 95% confidence region, identify Slamf1 (encoding signaling lymphocyte activation molecule) and Slamf6 (encoding Ly108) as potential candidates, and demonstrate retarded signaling lymphocyte activation molecule expression during T cell development of NOD mice, resulting in reduced expression at the CD4(+)CD8(+) stage, which is consistent with decreased NKT cell production and deranged tolerance induction in NOD mice.