Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.
Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.
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DOI：
10.3389/fimmu.2017.01386
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发表时间：
2017
影响因子：
7.3
通讯作者：
Futerman AH
中科院分区：
文献类型：
--
作者：
Saroha A;Pewzner-Jung Y;Ferreira NS;Sharma P;Jouan Y;Kelly SL;Feldmesser E;Merrill AH Jr;Trottein F;Paget C;Lang KS;Futerman AH
鞘脂（SL）在免疫系统中的作用最近受到越来越多的关注，这是由于这些重要的膜组分在调节各种免疫过程中发挥的新兴贡献。SL的酰基链长度在确定SL功能方面显得特别关键。在这里，我们展示了非常长的酰基链SL（VLC-SL）在胸腺中的不变自然杀伤T（iNKT）细胞成熟和肝脏中的稳态中的作用。缺乏VLC-SL的神经酰胺合酶2缺失小鼠对嗜肝性淋巴细胞性脉络丛脑膜炎病毒株易感，这是由于iNKT细胞数量减少。骨髓嵌合体实验表明，造血来源的VLC-SL对于胸腺中iNKT细胞的成熟至关重要，而实质来源的VLC-SL对于肝脏中iNKT细胞的存活和维持至关重要。我们的研究结果表明VLC-SL在iNKT细胞生理学中的关键作用。
The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (iNKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of iNKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of iNKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for iNKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in iNKT cell physiology.