Cutaneous RANK-RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans Cell Apoptosis.
Cutaneous RANK-RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans Cell Apoptosis.
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皮肤 RANK-RANKL 信号传导通过预防病毒诱导的朗格汉斯细胞凋亡来上调单纯疱疹病毒感染期间 CD8 介导的抗病毒免疫
DOI：
10.1038/jid.2015.225
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Loser K
中科院分区：
文献类型：
--
作者：
Klenner L;Hafezi W;Clausen BE;Lorentzen EU;Luger TA;Beissert S;Kühn JE;Loser K
单纯疱疹病毒1型（HSV-1）引起大多数皮肤病毒感染。病毒感染由免疫系统控制，CD 8+细胞毒性T淋巴细胞（CTL）已被证明在HSV-1感染的清除过程中至关重要。虽然表皮朗格汉斯细胞（LC）是第一个与病毒接触的树突状细胞（DC），研究表明，迁移性CD 103+真皮DC和CD 8 α+淋巴结驻留DC介导病毒抗原的加工和抗病毒CTL的分化。参与抗病毒免疫的调节，我们已经证明，通过NF-κB受体激活剂（RANK）及其配体RANKL的信号传导介导TcR的外周扩增。然而，除了扩增TcB外，RANK-RANKL相互作用还通过上调LCMV感染中CD 4+效应T细胞的启动或通过在克氏锥虫感染中产生寄生虫特异性CD 8 +T细胞参与抗菌免疫的控制。在这里，我们证明，皮肤RANK-RANKL信号传导是至关重要的诱导CD 8介导的抗病毒免疫反应，在HSV-1感染的皮肤，通过防止病毒诱导的LC凋亡，改善抗原转运到区域淋巴结，并增加淋巴结DC的CTL启动能力。
Herpes simplexvirus-type 1 (HSV-1) causes the majority of cutaneous viral infections. Viral infections are controlled by the immune system, and CD8+cytotoxic T-lymphocytes (CTLs) have been shown to be crucial during the clearance of HSV-1 infections. Although epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to come into contact with the virus, it has been shown that the processing of viral antigens and the differentiation of antiviral CTLs are mediated by migratory CD103+dermal DCs and CD8α+lymph node–resident DCs.In vivoregulatory T-cells (Tregs) are implicated in the regulation of antiviral immunity and we have shown that signaling via the receptor activator of NF-κB (RANK) and its ligand RANKL mediates the peripheral expansion of Tregs. However, in addition to expanding Tregs, RANK–RANKL interactions are involved in the control of antimicrobial immunity by upregulating the priming of CD4+effector T cells in LCMV infection or by the generation of parasite-specific CD8+T cells inTrypanosoma cruziinfection. Here, we demonstrate that cutaneous RANK–RANKL signaling is critical for the induction of CD8-mediated antiviral immune responses during HSV-1 infection of the skin by preventing virus-induced LC apoptosis, improving antigen transport to regional lymph nodes, and increasing the CTL priming capacity of lymph node DCs.
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DOI：
10.1084/jem.189.7.1025
发表时间：
1999-04-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bachmann MF;Wong BR;Josien R;Steinman RM;Oxenius A;Choi Y
通讯作者：
Choi Y
胚胎鸡器官培养物中角膜上皮和三叉神经突之间 1 型单纯疱疹病毒 (HSV-1) 的相互传播
DOI：
10.1096/fj.01-0803fje
发表时间：
2002
期刊：
The FASEB Journal
影响因子：
--
作者：
W. Hafezi;B. Eing;E. Lorentzen;S. Thanos;J. Kühn
通讯作者：
J. Kühn
皮肤朗格汉斯细胞在防御 HSV-1 感染中发挥重要作用
影响因子：
2.7
作者：
E. Sprecher;Y. Becker
通讯作者：
Y. Becker
影响因子：
64.8
作者：
Belkaid, Y;Piccirillo, CA;Sacks, DL
通讯作者：
Sacks, DL
影响因子：
5.4
作者：
Nandakumar, Subhadra;Woolard, Stacie N.;Kumaraguru, Uday
通讯作者：
Kumaraguru, Uday