Sulfatide-mediated activation of type II natural killer T cells prevents hepatic ischemic reperfusion injury in mice.
Sulfatide-mediated activation of type II natural killer T cells prevents hepatic ischemic reperfusion injury in mice.
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DOI：
10.1053/j.gastro.2010.10.003
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发表时间：
2011-02
期刊：
影响因子：
29.4
通讯作者：
Kumar V
中科院分区：
文献类型：
--
作者：
Arrenberg P;Maricic I;Kumar V
肝脏缺血再灌注损伤（IRI）是肝移植和肝脏切除术后的主要并发症。自然杀伤T（NKT）细胞在肝脏中占主导地位，它们识别与CD 1d分子结合的脂质抗原。I型NKT细胞利用半不变的T细胞受体并与α-半乳糖神经酰胺反应; II型NKT细胞利用不同的T细胞受体。一些II型NKT细胞识别自身糖脂硫苷脂。目前尚不清楚这些不同的NKT细胞亚群是否或如何介导IRI后的肝细胞损伤。我们研究了I型和II型NKT细胞在小鼠部分肝，热缺血和再灌注损伤中的作用。缺乏I型NKT细胞（Jα18−/−）的小鼠可免受肝脏IRI的影响，表现为肝细胞坏死和血清丙氨酸转氨酶水平降低。硫酸脂酶介导的II型NKT细胞的活化减少I型NKT细胞的IFN-γ分泌并防止IRI。通过硫苷脂介导的I型NKT细胞失活保护肝脏IRI与骨髓细胞亚群的肝脏募集显著减少相关，尤其是CD 11b +Gr-1 int、Gr-1−和NK细胞。在小鼠中，NKT细胞亚群在肝脏IRI中具有相反的作用：I型NKT细胞促进损伤，而硫酸脂反应性II型NKT细胞保护免受损伤。从小鼠到人类，NKT细胞的CD 1d活化是保守的，因此可以开发修改这些过程的策略来治疗肝再灌注损伤患者。
Hepatic ischemic reperfusion injury (IRI) is a major complication of liver transplantation and resectional hepatic surgeries. Natural killer T (NKT) cells predominate in liver, where they recognize lipid antigens bound to CD1d molecules. Type I NKT cells utilize a semi-invariant T-cell receptor and react with α-galactosylceramide; type II NKT cells use diverse T-cell receptors. Some type II NKT cells recognize the self-glycolipid sulfatide. It is not clear whether or how these distinct NKT cell subsets mediate hepatocellular damage following IRI. We examined the roles of type I and type II NKT cells in mice with partial hepatic, warm ischemia and reperfusion injury. Mice that lack type I NKT cells (Jα18−/−) were protected from hepatic IRI, indicated by reduced hepatocellular necrosis and serum levels of alanine aminotransferase. Sulfatide-mediated activation of type II NKT cells reduced IFN-γ secretion by type I NKT cells and prevented IRI. Protection from hepatic IRI by sulfatide-mediated inactivation of type I NKT cells was associated with significant reductions in hepatic recruitment of myeloid cell subsets, especially the CD11b+Gr-1int, Gr-1−, and NK cells. In mice, subsets of NKT cells have opposing roles in hepatic IRI: type I NKT cells promote injury whereas sulfatide-reactive type II NKT cells protect against injury. CD1d activation of NKT cells is conserved from mice to humans, so strategies to modify these processes might be developed to treat patients with hepatic reperfusion injury.
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DOI：
10.1084/jem.20061097
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lappas CM;Day YJ;Marshall MA;Engelhard VH;Linden J
通讯作者：
Linden J
影响因子：
15.9
作者：
Halder, Ramesh C.;Aguilera, Carlos;Kumar, Vipin
通讯作者：
Kumar, Vipin
通过靶向独特的无引起的CD1D反应T细胞群体对硫化物的反应性，预防自身免疫性。
影响因子：
15.3
作者：
Jahng, A;Maricic, I;Aguilera, C;Cardell, S;Halder, RC;Kumar, V
通讯作者：
Kumar, V
影响因子：
5.6
作者：
Arrenberg, Philomena;Halder, Ramesh;Kumar, Vipin
通讯作者：
Kumar, Vipin
影响因子：
0.9
作者：
Kupiec-Weglinski, JW;Busuttil, RW
通讯作者：
Busuttil, RW