Slam Haplotypes Modulate the Response to Lipopolysaccharide In Vivo through Control of NKT Cell Number and Function
Slam Haplotypes Modulate the Response to Lipopolysaccharide In Vivo through Control of NKT Cell Number and Function
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DOI：
10.4049/jimmunol.0902658
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Boyson, Jonathan E.
中科院分区：
文献类型：
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作者：
Aktan, Idil;Chant, Alan;Boyson, Jonathan E.
CD 1d限制性NKT细胞组成了一个先天性T细胞亚群，在放大先天免疫白细胞对TLR配体的反应中发挥作用。Slam基因座包含与先天性和适应性免疫反应有关的基因。在这项研究中，我们表明，不同的Slam基因座单倍型调节巨噬细胞的TLR 4配体LPS的反应，通过其控制的NKT细胞的数量和功能。与Slam单倍型-1（+）C57 BL/6 J小鼠中的巨噬细胞TNF产生相比，在响应体内LPS攻击时，Slam单倍型-2（+）129 S1/SvImJ和129 X1/SvJ小鼠中的巨噬细胞TNF产生显著受损。虽然没有观察到菌株之间的巨噬细胞对LPS的反应的细胞内在差异，但发现129只小鼠在肝脏NKT细胞数量、响应于CD 1d配体α-半乳糖神经酰胺的NKT细胞细胞因子产生以及体内LPS攻击后的NKT细胞IFN-γ产生方面存在缺陷。使用B6.129c1同源小鼠和过继转移，我们发现不同的Slam单倍型控制体内对LPS的反应，以及减少的NKT细胞数量和功能，并且这些表型与NKT细胞上信号淋巴细胞活化分子家族受体的差异表达相关。这些数据表明，区分两种Slam单倍型的多态性通过其对NKT细胞的作用显著调节体内先天免疫应答。免疫学杂志，2010，185：144-156。
CD1d-restricted NKT cells make up an innate-like T cell subset that plays a role in amplifying the response of innate immune leukocytes to TLR ligands. The Slam locus contains genes that have been implicated in innate and adaptive immune responses. In this study, we demonstrate that divergent Slam locus haplotypes modulate the response of macrophages to the TLR4 ligand LPS through their control of NKT cell number and function. In response to LPS challenge in vivo, macrophage TNF production in Slam haplotype-2(+) 129S1/SvImJ and 129X1/SvJ mice was significantly impaired in comparison with macrophage TNF production in Slam haplotype-1(+) C57BL/6J mice. Although no cell-intrinsic differences in macrophage responses to LPS were observed between strains, 129 mice were found to be deficient in liver NKT cell number, in NKT cell cytokine production in response to the CD1d ligand a-galactosylceramide, and in NKT cell IFN-gamma production after LPS challenge in vivo. Using B6.129c1 congenic mice and adoptive transfer, we found that divergent Slam haplotypes controlled the response to LPS in vivo, as well as the diminished NKT cell number and function, and that these phenotypes were associated with differential expression of signaling lymphocytic activation molecule family receptors on NKT cells. These data suggest that the polymorphisms that distinguish two Slam haplotypes significantly modulate the innate immune response in vivo through their effect on NKT cells. The Journal of Immunology, 2010, 185: 144-156.