The role of hepatic invariant NKT cells in systemic/local inflammation and mortality during polymicrobial septic shock.
The role of hepatic invariant NKT cells in systemic/local inflammation and mortality during polymicrobial septic shock.
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DOI：
10.4049/jimmunol.0801463
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发表时间：
2009-02-15
期刊：
影响因子：
--
通讯作者：
Ayala A
中科院分区：
文献类型：
--
作者：
Hu CK;Venet F;Heffernan DS;Wang YL;Horner B;Huang X;Chung CS;Gregory SH;Ayala A
自然杀伤T(NKT)4细胞被描述为“天然调节细胞”，因为它们对CD1d上的保守糖脂通过其不变的TCR产生快速反应。然而，对于肝脏NKT细胞在急性脓毒症攻击(盲肠结扎和穿孔；CLP)的局部和/或全身免疫反应中的作用，人们知之甚少。我们发现，不仅缺乏不变[I]NKT细胞(Jα18-/-)的小鼠的致死率显著降低，而且全身炎症反应也表现出减弱(对脾/腹膜免疫反应几乎没有影响)。流式细胞仪检测结果显示，C57BL/6J小鼠和Balb/c小鼠肝脏非实质细胞群中CD3+α、GalCer-CD1d-四聚体+细胞的百分率明显下降。这与这些细胞的显著激活(CD69和CD25的表达增加)以及Th1和Th2细胞内细胞因子阳性的NKT细胞的频率上升有关。在这方面，我们观察到，当小鼠在体内用抗CD1d封闭抗体预处理时，这不仅抑制了脓毒症小鼠全身IL-6和IL-10水平的上升，并改善了整个脓毒症小鼠的生存状况，而且这种治疗对CLP诱导的肝巨噬细胞IL-6和IL-10表达的变化也有相反的影响。综上所述，这些发现表明，肝脏iNKT细胞的激活在调节先天性免疫/全身炎症反应和急性感染性休克模型的生存中起着关键作用。
Natural killer T (NKT)4 cells have been described as “innate regulatory cells” because of their rapid response to conserved glycolipids presented on CD1d via their invariant TCR. However, little is known about the contribution of the hepatic NKT cell to the development of a local and/or systemic immune response to acute septic challenge (cecal ligation & puncture; CLP). We found not only that mice deficient in invariant [i] NKT cells (Jα18 -/-) had a marked attenuation in CLP induced mortality, but also exhibited an oblation of the systemic inflammatory response (with little effect on splenic/ peritoneal immune responsiveness). Flow cytometric data indicated that following CLP, there was a marked decline in the % of CD3+αGalCer-CD1d-tetramer+ cells in the mouse C57BL/6J and Balb/c liver non-parenchymal cell population. This was associated with the marked activation of these cells (increased expression of CD69 and CD25) as well as a rise in the frequency of NKT cells positive for both Th1 and Th2 intracellular cytokines. In this respect, when mice were pre-treated in vivo with anti-CD1d blocking antibody we observed not only that this inhibited the systemic rise of IL-6 and IL-10 levels in septic mice and improved overall septic survival, but that the CLP induced changes in liver macrophage IL-6 and IL-10 expressions were inversely effected by this treatment. Together, these findings suggest that the activation of hepatic iNKT cells plays a critical role in regulating the innate immune/ systemic inflammatory response and survival in a model of acute septic shock.
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影响因子：
4.4
作者：
Chen, YG;Choisy-Rossi, CM;Serreze, DV
通讯作者：
Serreze, DV
DOI：
10.1097/00005373-199604000-00008
发表时间：
1996-04-01
影响因子：
--
作者：
Ayala, A;Urbanich, MA;Chaudry, IH
通讯作者：
Chaudry, IH
影响因子：
3.8
作者：
AYALA, A;PERRIN, MM;CHAUDRY, IH
通讯作者：
CHAUDRY, IH
DOI：
10.1084/jem.169.6.2021
发表时间：
1989-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cross AS;Sadoff JC;Kelly N;Bernton E;Gemski P
通讯作者：
Gemski P
影响因子：
15.3
作者：
Benlagha, K;Weiss, A;Beavis, A;Teyton, L;Bendelac, A
通讯作者：
Bendelac, A