Early IL-17 production by intrahepatic T cells is important for adaptive immune responses in viral hepatitis.
Early IL-17 production by intrahepatic T cells is important for adaptive immune responses in viral hepatitis.
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DOI：
10.4049/jimmunol.1201970
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发表时间：
2013-01-15
期刊：
影响因子：
--
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Hou L;Jie Z;Desai M;Liang Y;Soong L;Wang T;Sun J
本研究旨在探究急性病毒性肝炎期间肝实质固有免疫和适应性免疫成分之间的相互作用。小鼠经静脉感染重组腺病毒，在感染后的最初24小时内，我们发现肝脏中白细胞介素 - 17（IL - 17）和白细胞介素 - 23（IL - 23）有短暂但显著的积聚。体内中和这些白细胞介素可减轻肝脏损伤。进一步研究表明，IL - 17中和阻止了细胞毒性T淋巴细胞（CTL）和辅助性T细胞1（Th1）在肝内的积聚。肝脏中产生IL - 17的细胞大多数是γδ T细胞。此外，肝内IL - 17⁺γδ T细胞（而非干扰素 - γ⁺的细胞）在其表面优先表达白细胞介素 - 7受体α（IL - 7Rα，CD127），这与感染后12小时肝细胞来源的IL - 7升高相符。体内阻断IL - 7Rα严重阻碍病毒感染后产生IL - 17的细胞的扩增。在体外，IL - 7与IL - 23协同作用，并在T细胞受体γδ（TCRγδ）刺激下直接刺激γδ T细胞产生IL - 17。最后，发现I型干扰素（IFN - I）信号传导对肝脏IL - 7的诱导至关重要。总之，这些结果表明IFN - I/IL - 7/IL - 17级联在启动肝脏中的T细胞应答方面很重要。此外，肝细胞与固有免疫细胞和适应性免疫细胞之间高度协调的相互作用在肝炎的抗病毒免疫中起关键作用。
This study was conducted to examine the interactions among the innate and adaptive immune components of the liver parenchyma during acute viral hepatitis. Mice were i.v. infected with a recombinant adenovirus, and within the first 24 h of infection, we found a transient, but significant, accumulation of IL-17 and IL-23 in the liver. In vivo neutralization of these interleukins alleviated the liver injury. Further investigations showed that IL-17 neutralization halted the intrahepatic accumulation of CTL and Th1 cells. A majority of the IL-17-producing cells in the liver were γδ T cells. Additionally, intrahepatic IL-17+ γδ T cells, but not the IFN-γ+ ones, preferentially expressed IL-7Rα (CD127) on their surface, which coincided with an elevation of hepatocyte-derived IL-7 at 12 h post-infection. IL-7Rα blockade in vivo severely impeded the expansion of IL-17-producing cells following viral infection. In vitro, IL-7 synergized with IL-23 and directly stimulated IL-17 production from γδ T cells in response to TCRγδ stimulation. Finally, type I interferon (IFN-I) signaling was found to be critical for hepatic IL-7 induction. Collectively, these results showed that the IFN-I/IL-7/IL-17 cascade was important in priming T cell responses in the liver. Moreover, the highly coordinated cross talk among hepatocytes and innate and adaptive immune cells played a critical role in antiviral immunity in hepatitis.
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影响因子：
15.9
作者：
Bowen, DG;Zen, M;Bertolino, P
通讯作者：
Bertolino, P
I型，I型干扰素介导的肝炎病毒蛋白在小鼠肝脏中的自噬运输。
影响因子：
29.4
作者：
Desai MM;Gong B;Chan T;Davey RA;Soong L;Kolokoltsov AA;Sun J
通讯作者：
Sun J
DOI：
10.1111/j.1600-6143.2011.03458.x
发表时间：
2011-04
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Basha HI;Subramanian V;Seetharam A;Nath DS;Ramachandran S;Anderson CD;Shenoy S;Chapman WC;Crippin JS;Mohanakumar T
通讯作者：
Mohanakumar T
影响因子：
82.9
作者：
Liu, Xuebin;Leung, Stewart;Zhang, Jingwu Z.
通讯作者：
Zhang, Jingwu Z.
影响因子：
5.4
作者：
Ajuebor, Maureen N.;Chen, Qingling;Aw, Tak Yee
通讯作者：
Aw, Tak Yee