Interleukin-36β provides protection against HSV-1 infection, but does not modulate initiation of adaptive immune responses.
Interleukin-36β provides protection against HSV-1 infection, but does not modulate initiation of adaptive immune responses.
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DOI：
10.1038/s41598-017-05363-4
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发表时间：
2017-07-19
影响因子：
4.6
通讯作者：
Jensen LE
中科院分区：
文献类型：
--
作者：
Milora KA;Uppalapati SR;Sanmiguel JC;Zou W;Jensen LE
白细胞介素-36（IL-36）代表三种细胞因子，IL-36α、IL-36β和IL-36γ，它们与相同的受体IL-1 RL 2结合;然而，它们的生理功能仍然知之甚少。在此，使用侧腹皮肤感染小鼠模型来检查IL-36在针对HSV-1的免疫中的作用。表达分析显示，感染皮肤中IL-36α和IL-36β mRNA水平升高，而组成性IL-36γ水平基本保持不变。在人角质形成细胞中，IL-36α mRNA被HSV-1诱导，而IL-1β和TNFα增加所有三种IL-36 mRNA。人IL-36β mRNA的显性选择性剪接变体是亚型2，其是已知小鼠IL-36β mRNA的直系同源物。与野生型小鼠相比，IL-36β缺陷但IL-36α或IL-36γ不缺陷的小鼠死于HSV-1感染的频率更高。此外，IL-36β−/−小鼠沿着受感染的神经元出现更大的带状疱疹样皮肤病变。在野生型和IL-36β−/−小鼠中，HSV-1特异性抗体、CD 8+细胞和产生IFNγ的CD 4+细胞的水平在统计学上相等，表明两种毒株中获得性免疫的启动相似。这与野生型和IL-36β−/−小鼠中原发性皮肤病变中HSV-1基因组和mRNA水平开始下降的时间相关。我们的数据表明，IL-36β具有以前未被认识到的抗HSV-1感染的保护功能。
Interleukin-36 (IL-36) represents three cytokines, IL-36α, IL-36β and IL-36γ, which bind to the same receptor, IL-1RL2; however, their physiological function(s) remain poorly understood. Here, the role of IL-36 in immunity against HSV-1 was examined using the flank skin infection mouse model. Expression analyses revealed increased levels of IL-36α and IL-36β mRNA in infected skin, while constitutive IL-36γ levels remained largely unchanged. In human keratinocytes, IL-36α mRNA was induced by HSV-1, while IL-1β and TNFα increased all three IL-36 mRNAs. The dominant alternative splice variant of human IL-36β mRNA was isoform 2, which is the ortholog of the known mouse IL-36β mRNA. Mice deficient in IL-36β, but not IL-36α or IL-36γ, succumbed more frequently to HSV-1 infection than wild type mice. Furthermore, IL-36β−/− mice developed larger zosteriform skin lesions along infected neurons. Levels of HSV-1 specific antibodies, CD8+ cells and IFNγ-producing CD4+ cells were statistically equal in wild type and IL-36β−/− mice, suggesting similar initiation of adaptive immunity in the two strains. This correlated with the time at which HSV-1 genome and mRNA levels in primary skin lesions started to decline in both wild type and IL-36β−/− mice. Our data indicate that IL-36β has previously unrecognized functions protective against HSV-1 infection.
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DOI：
10.4049/jimmunol.1301481
发表时间：
2014-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Foster AM;Baliwag J;Chen CS;Guzman AM;Stoll SW;Gudjonsson JE;Ward NL;Johnston A
通讯作者：
Johnston A
影响因子：
8
作者：
通讯作者：
--
影响因子：
9.3
作者：
Bozoyan L;Dumas A;Patenaude A;Vallières L
通讯作者：
Vallières L
影响因子：
11.8
作者：
Knezevic, Aleksandra;Martic, Jelena;Jovanovic, Tanja
通讯作者：
Jovanovic, Tanja
影响因子：
4.8
作者：
Kumar, S;McDonnell, PC;Young, PR
通讯作者：
Young, PR